Tuesday, 18 December 2007
Dear Reader,
It is not often that our field receives recognition from the government so it was a pleasure to attend the investiture of Dr Stella Dalton as a Member in the General Division of the Order of Australia. This was undertaken by State Governor Professor Marie Bashir at Government House, Sydney on 21st September 2007.
Along with others who were commended for their bravery, philanthropy, public service or contributions to dentistry, medicine, Egyptology and other disciplines, Dr Dalton was recognised for her pioneering work in treating addictions using methadone when this was still in its infancy in 1969. As a psychiatrist, she recognised that addicts were not morally bereft but that some of them may progress well with prescribed doses of a safe, long acting opioid given under supervision with psychosocial supports.
Research in the meantime has proven her to be completely correct and now this treatment is being introduced into every corner of the globe to stem some of the most serious harms from drug addiction, most notably HIV/AIDS.
The ceremony was delightful and I just regret that I was not able to meet more of the distinguished Australians present. After the ceremony drinks and canapés were served in the beautiful gardens above the Sydney Opera House while a naval band played on. I met Professor Naguib Kanawati who had been honoured for his years of service to the field of Egyptology.
I join in others by saluting all these great Australians, including Dr Stella Dalton OA.
Andrew Byrne ..
12 December 2007
10 December 2007
Withdrawal management and detoxification.
Concord Seminar 25 September 2007
Topic: Withdrawal management and detoxification-with a focus on complicated patients. [Although this was based on a talk given by Dr Ferguson, the summary also includes audience discussion and input from the three authors.]
Dr Ferguson stressed that the McKinnon Unit is not a �detoxification� ward but a medical unit which manages drug and alcohol withdrawals. The term detoxification is commonly used to refer to "chemicals, drugs, and food additives in the processed foods that we eat....", so that the general public, as well as our patients, may conceptualise drug withdrawal as a removal of such toxins: bringing to mind colonic irrigation, detox diets like Lemon Detox, herbal laxatives and high-fibre diets eliminating caffeine, meat and processed food, and associated treatments such as lymphatic drainage and massage.
Dr Ferguson used clinical cases to illustrate principles and pitfalls of withdrawal management. Since this is often undertaken in private with minimal problems and no interventions at all, she chose to deal with the more complicated cases such as those with dual diagnosis, dual or triple dependency and/or chronic illnesses.
The first case was a 47 year old labourer who had relapsed after 3 years opioid abstinence. On presentation he was using MS Contin (slow-release morphine) 100mg to 500mg injected each day, to a maximum of up to 800mg in the 16 hrs before admission, with no withdrawal symptoms. He was also taking 10-15 x 5mg diazepam tabs daily (50-75mg daily). He was agitated and tremulous on arrival at the detox unit.
The early signs of irritability, anxiety and enlarged pupils (possibly due to general sympathomimetic arousal) were attributed to benzodiazepine withdrawal, where onset of symptoms is typically after 16 hours or so. Tremor is unusual as a symptom of opioid withdrawal, and might help point to benzodiazepine withdrawal.
The benzodiazepine withdrawal regime at McKinnon Unit is to give 20mg diazepam 2nd hourly, to a maximum of 80mg in 24 hours, reducing to 60mg daily, then 35mg daily, 20mg daily then nil. Dr Ferguson told us that formal scoring of benzodiazepine withdrawal has not been shown to have any predictive value.
Regarding opiate withdrawal there are usually early signs such as enlarged pupils, sweating, pallor, agitation, goose flesh, lacrimation and runny nose. After that, nausea, melancholia and hyperalgesia can occur. At 36-48 hours, abdominal cramps, nausea, diarrhoea, mild leg aches are seen. By this stage, the enlarged pupils usually settle. Beyond this time, at 48-72 hours, there is more prominent aching of the leg and back muscles, abdominal pain and diarrhoea.
For opiate withdrawals at McKinnon Unit the regimen is to give buprenorphine sub-lingual tablets 4mg +4mg+4mg in the first 24 hours. However, with a poor response to this drug initially, this patient needed a further 4mg making 16mg in the first day off heroin. (four-times daily buprenorphine dosing has more to do with service related issues than evidence base).
In this case the patient suffered a protracted withdrawal syndrome, with the need to reintroduce buprenorphine on day 11. This was probably due to the mixed withdrawal syndrome, and possibly inadequately treatment of the opioid withdrawals early on. It may be that buprenorphine doesn't quite have the "grunt" to provide adequate symptom control in some patients.
The second case was a 24 year old methamphetamine-dependent man with schizophrenia, who lived with his family and was on disability support pension. He was taking quetiapine (Seroquel) 600mg bd, amisolpride (Solian) 800mg daily, citalopram (Cipramil) 40 mg daily, and had also been smoking a gram of �ice� daily for 8 months and taking alprazolam (Xanax) 2mg bd � prescribed by a GP.
Withdrawal symptoms of agitation, hallucinations and religious preoccupation settled with diazepam 60mg in 24 hours. He then slept, was quiet and left against medical advice after 4 days, clearly unhappy with continuing treatment (and diazepam had been reduced significantly by then).
Dr Ferguson posed the question of whether there is a withdrawal period from amphetamine use at all, or whether it is just a �recovery period�. Hence symptomatic treatment for agitation and sleeplessness may be provided with medications such as chlorpromazine, olanzapine and/or diazepam: there is some evidence of amphetamine users accessing olanzapine (Zyprexa), as well as the more commonly available benzodiazepines, for self-medication of the amphetamine "come-down". The only thing known to help profound listlessness would be to extend the stimulant use, something Australian doctors are mostly not yet comfortable doing. However, the period of �come-down� is always self limited if the patient can remain drug free.
The third case was a man aged 45 yrs with hep C, cirrhosis, diabetes and leg ulcers who had been drinking 90 to 120g alcohol daily with up to 15 x 5mg tabs diazepam daily. Single and on a pension, he was still looking after his 13 year old daughter. He was a heavy tobacco smoker as well as using injected heroin every 2 weeks on �pay day�.
The case illustrated how comorbid medical problems can have similar signs to alcohol withdrawal, including elevation of body temperature, and how to discriminate with a proper medical evaluation including blood counts and biochemical measures. Other issues were the need for nicotine replacement for tobacco withdrawal; whether agitation might be due to nicotine replacement or nicotine withdrawal; possible advantages of oxazepam over diazepam for severe liver failure with impaired hepatic drug metabolism (risk of over-sedation from accumulation of diazepam); a lower need for diazepam when unwell or drowsy.
A mild Alcohol Withdrawal Syndrome may not need any medication within the first 24 hours, after 2-3 days symptoms of anxiety, sweaty, headaches, insomnia, tremor, mild hypertension and tachycardia may be present. �Generally symptoms are mild and require little in way of medication� however medication eases withdrawal and improves outcomes - diazepam and thiamine are the mainstay. There is no evidence of benefit from more than 100mg thiamine daily, however at least the first dose should be given intramuscularly, as after heavy alcohol use there may be chronic or acute diarrhoea, and oral absorption is often poor. For severe intoxication / withdrawal, for example for drinkers of methylated spirits, 100mg thiamine should be given intramuscularly for at least 3 days.
More severe symptoms are dehydration, diarrhoea, anorexia, nausea, vomiting and weakness and very severe cases may have hypertension (diastolic of 120mmHg or greater can require antihypertensives) panic attacks, marked tremors, fever (however true fever is rare unless with an infectious cause). Seizures and delirium are a sign of treatment failure and should not occur when proper medical treatment available.
Alcohol withdrawals can occur with relatively high blood alcohol levels in heavy drinkers, including those who have reduced their use, so one needs to assess baseline use and more recent use.
Alcohol Withdrawal Scales (AWS) are subjective, with infection/fever and other illnesses as potential confounders, and need to be used thoughtfully and in context. Further, AWS has poor correlation with BP/pulse. Providing diazepam only when AWS >5 means people can be significantly uncomfortable before can get treatment. A kinder alternative may be to treat as soon as the BP is elevated or at the first sign of tremor.
The issue of using vigabantrin (Sabril) for alcohol withdrawal was raised as it may have fewer side effects but is currently only approved for resistant epilepsy.
A fourth case was then described of recurrent withdrawal episodes in a 47 year old alcohol and opiate dependent man on pension living alone in a rental flat, a history of depression and hypothyroidism, and more than 10 admissions to hospitals in 12 months, usually through casualty distressed and unable to cope, out of medication in withdrawal, anxious, but also with several falls and injuries, complicated by MRSA infection, and recently shortness of breath with a possible myocardial infarction.
After prolonged withdrawals (80mgs diazepam for 3 days then reducing over 10 days) he was unable to go to rehabilitation as he was overwhelmed and unable to organise himself.
Issues raise by this case were: therapeutic nihilism - where feelings of despair, hopelessness in treatment providers augment the client's feelings of guilt, shame and hopelessness; and the �GOMER� (get out of my emergency room) syndrome. The patient had some cognitive impairment but not so much to need involvement of the Guardianship Board to manage his affairs. Under the NSW Inebriates Act there has been a trial at Nepean Hospital of compulsory treatment for 2 weeks, with another 2 weeks following where necessary. Patients can also be sent to gazetted Psychiatric Hospital beds. This is not feasible for the great majority.
In general the patient needs to initiate treatment, and we need to recognise and accept the limits of what we can do, focus on symptom management not demand management and have a clear consensus of treatment aims, an agreed plan of treatment and a opt out phase.
Dr Ferguson described protocols for withdrawal management at Rozelle Hospital.
Opiate dependency: - buprenorphine 8-12 mg sublingual per day for 3-5 days, depending on opiate type and quantity. Reduce to 8/6/4/2/2 for last 2days. Symptomatic relief with metoclopramide (Maxalon), hyosine (Buscopan), diazepam (Valium).
Alcohol: - diazepam (Valium), dose not set, related to dispensing and review issues, maybe 40mg/day and metoclopramide (Maxolon) and antihypertensive.
Cannabis/THC: Symptoms of insomnia, agitation, irritable, appetite change, lasting 1-5 days, for which benzodiazepines - at lower doses than for alcohol withdrawal - , olanzapine (Zyprexa), mirtazapine (Avanza) may be used. There seems to be a consensus not to do inpatient withdrawal for THC, but McKinnon will do it for failed (and well documented) outpatient withdrawal.
In order to access their services, there needs to be a phone assessment of demographics (do they live in the right area?); drug use and co-morbidities; negotiation of a treatment plan (which MAY include withdrawal medication options) and then articulation of the plan: for admission (the person must phone daily at 7am until they can secure a place for admission); and/or outpatient appointments; documentation for MMT/BMT; mental health assessment; and/or other requirements eg plans for subsequent rehabilitation programs.
Some predictors of failure ambulatory treatment (as an outpatient) are (1) poor support of abstinence; (2) poor housing (or no housing); (3) multiple drug use, including withdrawal from one substance and use of others (except nicotine); (4) or severe symptoms of withdrawal.
The question was raised why drug and alcohol practitioners in the community may have difficulty "referring" their patients to "detox" units, and do not receive discharge summaries as from most other hospital services. One answer may lie in the historical development of hospital drug and alcohol services using a psychiatric care model, with a primary client orientation and team based case, as well as possibly some resistance among nursing staff to perceived medical paternalism. Another may be that referring doctors have not acquainted themselves with the protocols of the "detox" unit.
In the second half there were a few case vignettes and selected scenarios:
"I went into hospital to come off alcohol and benzos, and they just gave me Normison and sent me home on the 3rd day ...". This was a 41yo woman with history of alcohol withdrawal fits, alcoholic hepatitis. Some questions raised were:
1. If someone has a history of having fits while taking benzodiazepines, do they need admission for withdrawal management? A. not necessarily
2. Why does anyone need to go into a detox unit to come off benzodiazepines? Surely you can just change them over to diazepam and reduce the dose, in the community. A: supervision issues.
Evidently this patient�s symptoms were assessed as mild in the first 48 hours, predicting little risk of complicated benzodiazepine withdrawal. However it appears to be an early discharge for alcohol withdrawal, depending on the alcohol use history given.
"I get fits when I stop alcohol, but I'm not going back to that detox place - can't you just give me some Valium, Doc?" This was a 54 yo man on methadone, with hepatitis C, cirrhosis and ascites, presenting to a doctor in the community, with blood alcohol 0.06 and withdrawal symptoms of agitation and marked tremor. As alcohol withdrawal is dangerous, Dr Ferguson considered it medically strongly indicated to give some diazepam. However, some doctors may feels apprehensive about medico-legal consequences of giving diazepam to an intoxicated patient outside a supervised setting. It may be safest in small quantities, especially if supervised at the surgery, clinic or pharmacy.
"I need to go somewhere to come off cannabis, but the rehab won't take me because I'm on methadone, and the detox unit say they don't do cannabis withdrawal...." - it was agreed that some people may need to remove themselves from a high exposure environment to stop cannabis use, and this may be difficult when the person in on MMT. Some "detox" units offer this service, while for others it is considered low priority.
Andrew Byrne posed the question of when and why detoxification units started giving opiates to opiate addicts. Previously it was rather unusual, if not unheard of, rather like giving hospital brandy to alcoholics who were drying out. This changed the nature of the treatment from detoxification to �re-toxification� in many or even most opiate admissions. This can even be the case in those intent on short-term abstinence. Especially with a very long acting drug such as buprenorphine, it ensures that detoxification does not even start until a few days after leaving the ward, quite the opposite of the traditional position. The practice does offer patients a �taste� of one maintenance treatment yet this they could just as easily obtain as out-patients, and most opiate addicts have tried such approaches already. This change in treatment policy seems to have happened without any discussion or most importantly, input from drug users themselves. Dr Ferguson explained that compliance and retention are now better after the introduction of buprenorphine. Yet it is hard to understand how this brings patients closer to the goal of opiate abstinence.
Presenter: Dr Joanne Ferguson, FRANZCP, FAChAM, staff specialist psychiatrist, Rozelle Hospital. Medical Director, McKinnon Unit.
Topic: Withdrawal management and detoxification-with a focus on complicated patients. [Although this was based on a talk given by Dr Ferguson, the summary also includes audience discussion and input from the three authors.]
Dr Ferguson stressed that the McKinnon Unit is not a �detoxification� ward but a medical unit which manages drug and alcohol withdrawals. The term detoxification is commonly used to refer to "chemicals, drugs, and food additives in the processed foods that we eat....", so that the general public, as well as our patients, may conceptualise drug withdrawal as a removal of such toxins: bringing to mind colonic irrigation, detox diets like Lemon Detox, herbal laxatives and high-fibre diets eliminating caffeine, meat and processed food, and associated treatments such as lymphatic drainage and massage.
Dr Ferguson used clinical cases to illustrate principles and pitfalls of withdrawal management. Since this is often undertaken in private with minimal problems and no interventions at all, she chose to deal with the more complicated cases such as those with dual diagnosis, dual or triple dependency and/or chronic illnesses.
The first case was a 47 year old labourer who had relapsed after 3 years opioid abstinence. On presentation he was using MS Contin (slow-release morphine) 100mg to 500mg injected each day, to a maximum of up to 800mg in the 16 hrs before admission, with no withdrawal symptoms. He was also taking 10-15 x 5mg diazepam tabs daily (50-75mg daily). He was agitated and tremulous on arrival at the detox unit.
The early signs of irritability, anxiety and enlarged pupils (possibly due to general sympathomimetic arousal) were attributed to benzodiazepine withdrawal, where onset of symptoms is typically after 16 hours or so. Tremor is unusual as a symptom of opioid withdrawal, and might help point to benzodiazepine withdrawal.
The benzodiazepine withdrawal regime at McKinnon Unit is to give 20mg diazepam 2nd hourly, to a maximum of 80mg in 24 hours, reducing to 60mg daily, then 35mg daily, 20mg daily then nil. Dr Ferguson told us that formal scoring of benzodiazepine withdrawal has not been shown to have any predictive value.
Regarding opiate withdrawal there are usually early signs such as enlarged pupils, sweating, pallor, agitation, goose flesh, lacrimation and runny nose. After that, nausea, melancholia and hyperalgesia can occur. At 36-48 hours, abdominal cramps, nausea, diarrhoea, mild leg aches are seen. By this stage, the enlarged pupils usually settle. Beyond this time, at 48-72 hours, there is more prominent aching of the leg and back muscles, abdominal pain and diarrhoea.
For opiate withdrawals at McKinnon Unit the regimen is to give buprenorphine sub-lingual tablets 4mg +4mg+4mg in the first 24 hours. However, with a poor response to this drug initially, this patient needed a further 4mg making 16mg in the first day off heroin. (four-times daily buprenorphine dosing has more to do with service related issues than evidence base).
In this case the patient suffered a protracted withdrawal syndrome, with the need to reintroduce buprenorphine on day 11. This was probably due to the mixed withdrawal syndrome, and possibly inadequately treatment of the opioid withdrawals early on. It may be that buprenorphine doesn't quite have the "grunt" to provide adequate symptom control in some patients.
The second case was a 24 year old methamphetamine-dependent man with schizophrenia, who lived with his family and was on disability support pension. He was taking quetiapine (Seroquel) 600mg bd, amisolpride (Solian) 800mg daily, citalopram (Cipramil) 40 mg daily, and had also been smoking a gram of �ice� daily for 8 months and taking alprazolam (Xanax) 2mg bd � prescribed by a GP.
Withdrawal symptoms of agitation, hallucinations and religious preoccupation settled with diazepam 60mg in 24 hours. He then slept, was quiet and left against medical advice after 4 days, clearly unhappy with continuing treatment (and diazepam had been reduced significantly by then).
Dr Ferguson posed the question of whether there is a withdrawal period from amphetamine use at all, or whether it is just a �recovery period�. Hence symptomatic treatment for agitation and sleeplessness may be provided with medications such as chlorpromazine, olanzapine and/or diazepam: there is some evidence of amphetamine users accessing olanzapine (Zyprexa), as well as the more commonly available benzodiazepines, for self-medication of the amphetamine "come-down". The only thing known to help profound listlessness would be to extend the stimulant use, something Australian doctors are mostly not yet comfortable doing. However, the period of �come-down� is always self limited if the patient can remain drug free.
The third case was a man aged 45 yrs with hep C, cirrhosis, diabetes and leg ulcers who had been drinking 90 to 120g alcohol daily with up to 15 x 5mg tabs diazepam daily. Single and on a pension, he was still looking after his 13 year old daughter. He was a heavy tobacco smoker as well as using injected heroin every 2 weeks on �pay day�.
The case illustrated how comorbid medical problems can have similar signs to alcohol withdrawal, including elevation of body temperature, and how to discriminate with a proper medical evaluation including blood counts and biochemical measures. Other issues were the need for nicotine replacement for tobacco withdrawal; whether agitation might be due to nicotine replacement or nicotine withdrawal; possible advantages of oxazepam over diazepam for severe liver failure with impaired hepatic drug metabolism (risk of over-sedation from accumulation of diazepam); a lower need for diazepam when unwell or drowsy.
A mild Alcohol Withdrawal Syndrome may not need any medication within the first 24 hours, after 2-3 days symptoms of anxiety, sweaty, headaches, insomnia, tremor, mild hypertension and tachycardia may be present. �Generally symptoms are mild and require little in way of medication� however medication eases withdrawal and improves outcomes - diazepam and thiamine are the mainstay. There is no evidence of benefit from more than 100mg thiamine daily, however at least the first dose should be given intramuscularly, as after heavy alcohol use there may be chronic or acute diarrhoea, and oral absorption is often poor. For severe intoxication / withdrawal, for example for drinkers of methylated spirits, 100mg thiamine should be given intramuscularly for at least 3 days.
More severe symptoms are dehydration, diarrhoea, anorexia, nausea, vomiting and weakness and very severe cases may have hypertension (diastolic of 120mmHg or greater can require antihypertensives) panic attacks, marked tremors, fever (however true fever is rare unless with an infectious cause). Seizures and delirium are a sign of treatment failure and should not occur when proper medical treatment available.
Alcohol withdrawals can occur with relatively high blood alcohol levels in heavy drinkers, including those who have reduced their use, so one needs to assess baseline use and more recent use.
Alcohol Withdrawal Scales (AWS) are subjective, with infection/fever and other illnesses as potential confounders, and need to be used thoughtfully and in context. Further, AWS has poor correlation with BP/pulse. Providing diazepam only when AWS >5 means people can be significantly uncomfortable before can get treatment. A kinder alternative may be to treat as soon as the BP is elevated or at the first sign of tremor.
The issue of using vigabantrin (Sabril) for alcohol withdrawal was raised as it may have fewer side effects but is currently only approved for resistant epilepsy.
A fourth case was then described of recurrent withdrawal episodes in a 47 year old alcohol and opiate dependent man on pension living alone in a rental flat, a history of depression and hypothyroidism, and more than 10 admissions to hospitals in 12 months, usually through casualty distressed and unable to cope, out of medication in withdrawal, anxious, but also with several falls and injuries, complicated by MRSA infection, and recently shortness of breath with a possible myocardial infarction.
After prolonged withdrawals (80mgs diazepam for 3 days then reducing over 10 days) he was unable to go to rehabilitation as he was overwhelmed and unable to organise himself.
Issues raise by this case were: therapeutic nihilism - where feelings of despair, hopelessness in treatment providers augment the client's feelings of guilt, shame and hopelessness; and the �GOMER� (get out of my emergency room) syndrome. The patient had some cognitive impairment but not so much to need involvement of the Guardianship Board to manage his affairs. Under the NSW Inebriates Act there has been a trial at Nepean Hospital of compulsory treatment for 2 weeks, with another 2 weeks following where necessary. Patients can also be sent to gazetted Psychiatric Hospital beds. This is not feasible for the great majority.
In general the patient needs to initiate treatment, and we need to recognise and accept the limits of what we can do, focus on symptom management not demand management and have a clear consensus of treatment aims, an agreed plan of treatment and a opt out phase.
Dr Ferguson described protocols for withdrawal management at Rozelle Hospital.
Opiate dependency: - buprenorphine 8-12 mg sublingual per day for 3-5 days, depending on opiate type and quantity. Reduce to 8/6/4/2/2 for last 2days. Symptomatic relief with metoclopramide (Maxalon), hyosine (Buscopan), diazepam (Valium).
Alcohol: - diazepam (Valium), dose not set, related to dispensing and review issues, maybe 40mg/day and metoclopramide (Maxolon) and antihypertensive.
Cannabis/THC: Symptoms of insomnia, agitation, irritable, appetite change, lasting 1-5 days, for which benzodiazepines - at lower doses than for alcohol withdrawal - , olanzapine (Zyprexa), mirtazapine (Avanza) may be used. There seems to be a consensus not to do inpatient withdrawal for THC, but McKinnon will do it for failed (and well documented) outpatient withdrawal.
In order to access their services, there needs to be a phone assessment of demographics (do they live in the right area?); drug use and co-morbidities; negotiation of a treatment plan (which MAY include withdrawal medication options) and then articulation of the plan: for admission (the person must phone daily at 7am until they can secure a place for admission); and/or outpatient appointments; documentation for MMT/BMT; mental health assessment; and/or other requirements eg plans for subsequent rehabilitation programs.
Some predictors of failure ambulatory treatment (as an outpatient) are (1) poor support of abstinence; (2) poor housing (or no housing); (3) multiple drug use, including withdrawal from one substance and use of others (except nicotine); (4) or severe symptoms of withdrawal.
The question was raised why drug and alcohol practitioners in the community may have difficulty "referring" their patients to "detox" units, and do not receive discharge summaries as from most other hospital services. One answer may lie in the historical development of hospital drug and alcohol services using a psychiatric care model, with a primary client orientation and team based case, as well as possibly some resistance among nursing staff to perceived medical paternalism. Another may be that referring doctors have not acquainted themselves with the protocols of the "detox" unit.
In the second half there were a few case vignettes and selected scenarios:
"I went into hospital to come off alcohol and benzos, and they just gave me Normison and sent me home on the 3rd day ...". This was a 41yo woman with history of alcohol withdrawal fits, alcoholic hepatitis. Some questions raised were:
1. If someone has a history of having fits while taking benzodiazepines, do they need admission for withdrawal management? A. not necessarily
2. Why does anyone need to go into a detox unit to come off benzodiazepines? Surely you can just change them over to diazepam and reduce the dose, in the community. A: supervision issues.
Evidently this patient�s symptoms were assessed as mild in the first 48 hours, predicting little risk of complicated benzodiazepine withdrawal. However it appears to be an early discharge for alcohol withdrawal, depending on the alcohol use history given.
"I get fits when I stop alcohol, but I'm not going back to that detox place - can't you just give me some Valium, Doc?" This was a 54 yo man on methadone, with hepatitis C, cirrhosis and ascites, presenting to a doctor in the community, with blood alcohol 0.06 and withdrawal symptoms of agitation and marked tremor. As alcohol withdrawal is dangerous, Dr Ferguson considered it medically strongly indicated to give some diazepam. However, some doctors may feels apprehensive about medico-legal consequences of giving diazepam to an intoxicated patient outside a supervised setting. It may be safest in small quantities, especially if supervised at the surgery, clinic or pharmacy.
"I need to go somewhere to come off cannabis, but the rehab won't take me because I'm on methadone, and the detox unit say they don't do cannabis withdrawal...." - it was agreed that some people may need to remove themselves from a high exposure environment to stop cannabis use, and this may be difficult when the person in on MMT. Some "detox" units offer this service, while for others it is considered low priority.
Andrew Byrne posed the question of when and why detoxification units started giving opiates to opiate addicts. Previously it was rather unusual, if not unheard of, rather like giving hospital brandy to alcoholics who were drying out. This changed the nature of the treatment from detoxification to �re-toxification� in many or even most opiate admissions. This can even be the case in those intent on short-term abstinence. Especially with a very long acting drug such as buprenorphine, it ensures that detoxification does not even start until a few days after leaving the ward, quite the opposite of the traditional position. The practice does offer patients a �taste� of one maintenance treatment yet this they could just as easily obtain as out-patients, and most opiate addicts have tried such approaches already. This change in treatment policy seems to have happened without any discussion or most importantly, input from drug users themselves. Dr Ferguson explained that compliance and retention are now better after the introduction of buprenorphine. Yet it is hard to understand how this brings patients closer to the goal of opiate abstinence.
Summary of the evening written by Richard Hallinan, Andrew Byrne, Judith Meldrum with help from Dr Joanne Ferguson�s power point presentation.
4 December 2007
Advances in assessment and treatments for infection with hepatitis C virus (HCV)
Concord Seminar 20th November 2007
Topics: HCV epidemiology; treatment assessment; HCV treatment among methadone patients and current injecting drug users (IDU); strategies to improve HCV treatment outcomes; advances in HCV treatment and new research.
Although there has been a drop in annual HCV notifications in Australia from 15,000 in the mid 1990s to 13,000 recently, it is unsure how much of this reflects a fall in incidence (new infections) and thus a success for existing harm reduction policies. As most HCV infections in injecting drug users (IDU) occur within the first few years of injecting, some more significant indicators may be reductions in new HCV notifications in the 15-19 year age group, and in HCV prevalence in young male IDUs attending needle syringe programs (NSPs) from 2001-2006. Such figures do indeed show a marked reduction, which is reassuring that overall notifications should decline further.
It is possible that the lack of a fall in HCV prevalence in young female IDUs may reflect their "going second" in shared injecting situations, and/or sometimes having older male partners already at higher risk of having HCV.
IDUs still constituted the majority (62%) of all acute or newly acquired infections in Australia (n = 474 in 2006), however this may be an underestimate as the source of infection is reported as unknown in 15%, and sexual in 5% (sexual transmission may occur where sexual practices involve blood but is unlikely in most "vanilla" sexual encounters / relationships). Tattoos account for about 8% and occupational exposure 2.5% of new cases.
Overall HCV seroprevalence in people attending NSP remains high at 65%, and is somewhat higher again (75%) in MMT/BMT populations: ie about 30,000 of the circa 40,000 people in opioid replacement treatment in Australia. Of these, probably about 20,000 (50%) have chronic HCV (RNA-positive), about 10% of the total in Australia, making this an important point of access for HCV treatment.
Mortality among people with HCV in Australia has a bimodal distribution, in the 5th and 8th decades of life, the former largely related to drug-related deaths among IDUs and the latter liver disease-related deaths in people born overseas, in HCV endemic areas. Liver disease-related deaths have risen since 1999, a trend perhaps "unmasked" by a fall of direct drug-related deaths as a result of the "heroin shortage".
With cases of HCV cirrhosis in Australia predicted to rise to 12,000 by 2010, and twice that number by 2020, an aim is to be treating 6,000 people/year for HCV. Since April 2006, when the liver biopsy requirement for interferon-based treatment was dropped, treatment figures have risen from about 2,000 to 3,000/year. Liver biopsy was a major disincentive for many people.
Sustained viral response SVR (persisting absence of viral RNA 6 months after treatment) is usually considered a cure of the viral infection, although not necessarily of the underlying liver damage. Occasional later relapses of HCV may represent reinfection with HCV in IDU. Over the last decade response rates to interferon-based treatment have improved, from about 10% SVR for interferon monotherapy to overall to over 60% SVR for combined pegylated interferon/ribavirin (PEG-IFN/RBV), ranging from 50 � 80% depending on genotype.
Early studies of PEG-IFN�2a/RBV showed benefit of longer treatment (48 versus 24 weeks) and bodyweight-adjusted ribavirin dosing (up to 1200mg/day) for genotype 1, but not for genotypes 2 and 3. While early viral response (EVR) - defined as RNA undetectable or >99% decline in viral load at 12 weeks - increases the chances of SVR for genotype 1 to 72%, failure to achieve EVR almost inevitably predicts treatment failure.
The bottom line for treatment is: 24 weeks PEG-IFN/RBV for genotypes 2 and 3; 48 weeks for genotype 1 if the person achieves EVR at 12 weeks. There is no evidence of any difference in efficacy between PEG-IFN�2a (Roche) and PEG-IFN�2b (Schering-Plough).
Recent analysis suggests that people with genotype 1 who have a Rapid Viral Response (RVR) - HCV RNA undetectable at 4 weeks - may do just as well with 24 weeks as 48 weeks of PEG-IFN�2a/RBV, achieving SVR rates above 80%.
At St Vincent�s Hospital in Darlinghurst, treatment completion rates rose from 55% 2000-02 to 74% in 2003-04, with drops in treatment discontinuations due to both non-response and to toxicity. This appears a trend to improvements in delivery of treatment.
Results of treatment in current injectors are comparable to results among non injectors, and abstinence from IDU is not a pre-condition for subsidised treatment in Australia: nor are stage of fibrosis (was pre-2006); elevated ALT (was pre-2006); the presence of symptoms; low alcohol intake.
There is some evidence of poorer treatment outcomes in people who continue to drink alcohol, but whether this is related to worsened treatment adherence or effects on viral replication is unclear.
The current conditions for subsidised treatment eligibility in Australia (S100 Criteria) are:
� 18 years or older
� No evidence of de-compensated cirrhosis
� Must have chronic HCV infection (>6 months)
� Use double contraception where the patient is either a woman of child-bearing years or their male partner.
� No prior IFN-based HCV treatment
Subsidised treatment costs the patient about A$30/month, (A$5/month for concession card holders) and this is probably as cheap as anywhere in the world.
To be balanced against the curative potential of PEG-IFN/RBV are its toxicity (flu-like symptoms, depression, anaemia, lethargy) and the requirement for contraception during and 6 months following treatment. Apart from treatment eligibility, the stage of liver disease and prognosis the genotype and viral load, presence of co-morbidities, and work and family obligations have to be considered in treatment decision-making. There needs to be at least some treatment willingness and relative socio-behavioural stability, however with persistence and good support people with relative treatment contraindications can often be successfully brought through treatment.
Greg Dore advocates some targeting of individuals with higher risk of progressive disease:
Higher likelihood of cirrhosis is predicted by:
� older age (> 40 years)
� duration of infection > 20 years
� heavy alcohol intake
� HIV or chronic HBV coinfection
� peripheral stigmata of CLD (spider naevi, palmar erythema)
� impaired hepatic synthetic function (low albumin, prolonged PT)
� AST / ALT ratio > 1.0
� AST / platelet ratio > 1.0 (<0.5 very unlikely to have cirrhosis)
At the Byrne Surgery, about 50% of people with chronic HCV met similar criteria for higher risk of HCV progression, and have been specifically targeted for treatment, with 27 people having been treated since 2003. Of 20 liver biopsies among these higher risk people, 18 had at least moderate liver fibrosis.
Although HIV and HBV co-infection are relatively uncommon in people with HCV infection, they are definite indicators of higher risk, and in many cases HCV treatment should be undertaken before HIV or HBV treatment.
Phase II trials suggest benefit from triple therapies of IFN/RBV with protease inhibitors for chronic HCV and Phase II trials are due to start soon.
Acute HCV can be treated with interferon monotherapy, with SVR rates of 80-90% in 3 months treatment, unless there is HIV co-infection or HCV genotype 1 with a high viral load. However, as about 25% of people spontaneously clear the virus (generally in the first 3 months after infection but up to 6 months and even later in a few cases) treatment of acute infection is usually deferred at least 3 months.
Although sustained viral response rates at the Byrne surgery are high (71% overall, 81% for genotype 2/3) a case was presented to show that things are not always easy. This long-term MMT patient received HCV antiviral treatment in the setting of micronodular cirrhosis, Genotype 1a/1b, viral load 360,000 and pre-treatment alcohol use of 30-60g/day. This patient was overweight 105kg, a smoker (10 cigs/day) with shortness of breath on exertion, chronic airflow limitation (not taking medications), hypertension (Enalapril), probable ischaemic heart disease (chest tightness on stress test but no ECG changes; echocardiogram: LVH with moderate dilatation), osteoarthritis (diclofenac prn), a history of peptic ulcer disease (uses omeprazole prn).
Despite these relative contraindications to treatment, this patient ceased drinking alcohol, and started combination treatment with IFN.2a/RBV, achieving rapid viral response (<600 ie qualitative RNA assay) at 5 weeks. RBV dose started with 1200mg/day and reducing to 800mg/day as haemoglobin dropped under 100, and was stopped for 5 weeks when the patient suffered severe nosebleeds (with normal BP 130/80; prothrombin time 1.1 and platelets acceptable at 81). Diclofenac was ceased, and ENT review showed a large vessel on the septum which was cauterised, packed with Chloromycetin for 3 days, with ongoing Vaseline use.
After the patient had stoically endured 36 weeks of IFN.2a/RBV, and in view of the apparent rapid viral response, treatment was stopped at week 36, sadly with a rapid ALT and viral flare. The patient has since maintained alcohol abstinence and long term low dose interferon treatment is being considered.
Issues arising from this case were the feasibility of treatment of "brittle" patients; drying of the nasal mucosa with the IFN/RBV; the pros and cons of NSAIDS for osteoarthritis in this situation; the possibility of viral escape with the interruption to RBV treatment and the wisdom of the decision to stop treatment early; whether endoscopy might have been done to exclude oesophageal varices before treatment; the benefits of going on the front foot in treating HCV in substance dependent people, who may rise to the challenge by achieving abstinence (in this case alcohol abstinence).
Other questions arising in the second half:
Q. What about treating people with persistently high-normal ALT? A: there is some discussion about whether ALT reference ranges should be lowered, especially for women. A single normal ALT measurement is not helpful, as ALT typically waxes and wanes in chronic HCV, so ongoing monitoring at least is required. Although one would rather have a persistently lowish than a persistently very high ALT, ALT correlates poorly with disease activity, and the duration of HCV is an important consideration in assessing risk of disease progression.
Q. What is the role of abdominal ultrasound in assessing chronic HCV? A: mainly to exclude portal hypertension. Greg Dore often does not order this test. Newer methods for assessing fibrosis/cirrhosis by measuring the stiffness of the liver may make ultrasound more useful.
Presenter: Professor Greg Dore, Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research.
Topics: HCV epidemiology; treatment assessment; HCV treatment among methadone patients and current injecting drug users (IDU); strategies to improve HCV treatment outcomes; advances in HCV treatment and new research.
Although there has been a drop in annual HCV notifications in Australia from 15,000 in the mid 1990s to 13,000 recently, it is unsure how much of this reflects a fall in incidence (new infections) and thus a success for existing harm reduction policies. As most HCV infections in injecting drug users (IDU) occur within the first few years of injecting, some more significant indicators may be reductions in new HCV notifications in the 15-19 year age group, and in HCV prevalence in young male IDUs attending needle syringe programs (NSPs) from 2001-2006. Such figures do indeed show a marked reduction, which is reassuring that overall notifications should decline further.
It is possible that the lack of a fall in HCV prevalence in young female IDUs may reflect their "going second" in shared injecting situations, and/or sometimes having older male partners already at higher risk of having HCV.
IDUs still constituted the majority (62%) of all acute or newly acquired infections in Australia (n = 474 in 2006), however this may be an underestimate as the source of infection is reported as unknown in 15%, and sexual in 5% (sexual transmission may occur where sexual practices involve blood but is unlikely in most "vanilla" sexual encounters / relationships). Tattoos account for about 8% and occupational exposure 2.5% of new cases.
Overall HCV seroprevalence in people attending NSP remains high at 65%, and is somewhat higher again (75%) in MMT/BMT populations: ie about 30,000 of the circa 40,000 people in opioid replacement treatment in Australia. Of these, probably about 20,000 (50%) have chronic HCV (RNA-positive), about 10% of the total in Australia, making this an important point of access for HCV treatment.
Mortality among people with HCV in Australia has a bimodal distribution, in the 5th and 8th decades of life, the former largely related to drug-related deaths among IDUs and the latter liver disease-related deaths in people born overseas, in HCV endemic areas. Liver disease-related deaths have risen since 1999, a trend perhaps "unmasked" by a fall of direct drug-related deaths as a result of the "heroin shortage".
With cases of HCV cirrhosis in Australia predicted to rise to 12,000 by 2010, and twice that number by 2020, an aim is to be treating 6,000 people/year for HCV. Since April 2006, when the liver biopsy requirement for interferon-based treatment was dropped, treatment figures have risen from about 2,000 to 3,000/year. Liver biopsy was a major disincentive for many people.
Sustained viral response SVR (persisting absence of viral RNA 6 months after treatment) is usually considered a cure of the viral infection, although not necessarily of the underlying liver damage. Occasional later relapses of HCV may represent reinfection with HCV in IDU. Over the last decade response rates to interferon-based treatment have improved, from about 10% SVR for interferon monotherapy to overall to over 60% SVR for combined pegylated interferon/ribavirin (PEG-IFN/RBV), ranging from 50 � 80% depending on genotype.
Early studies of PEG-IFN�2a/RBV showed benefit of longer treatment (48 versus 24 weeks) and bodyweight-adjusted ribavirin dosing (up to 1200mg/day) for genotype 1, but not for genotypes 2 and 3. While early viral response (EVR) - defined as RNA undetectable or >99% decline in viral load at 12 weeks - increases the chances of SVR for genotype 1 to 72%, failure to achieve EVR almost inevitably predicts treatment failure.
The bottom line for treatment is: 24 weeks PEG-IFN/RBV for genotypes 2 and 3; 48 weeks for genotype 1 if the person achieves EVR at 12 weeks. There is no evidence of any difference in efficacy between PEG-IFN�2a (Roche) and PEG-IFN�2b (Schering-Plough).
Recent analysis suggests that people with genotype 1 who have a Rapid Viral Response (RVR) - HCV RNA undetectable at 4 weeks - may do just as well with 24 weeks as 48 weeks of PEG-IFN�2a/RBV, achieving SVR rates above 80%.
At St Vincent�s Hospital in Darlinghurst, treatment completion rates rose from 55% 2000-02 to 74% in 2003-04, with drops in treatment discontinuations due to both non-response and to toxicity. This appears a trend to improvements in delivery of treatment.
Results of treatment in current injectors are comparable to results among non injectors, and abstinence from IDU is not a pre-condition for subsidised treatment in Australia: nor are stage of fibrosis (was pre-2006); elevated ALT (was pre-2006); the presence of symptoms; low alcohol intake.
There is some evidence of poorer treatment outcomes in people who continue to drink alcohol, but whether this is related to worsened treatment adherence or effects on viral replication is unclear.
The current conditions for subsidised treatment eligibility in Australia (S100 Criteria) are:
� 18 years or older
� No evidence of de-compensated cirrhosis
� Must have chronic HCV infection (>6 months)
� Use double contraception where the patient is either a woman of child-bearing years or their male partner.
� No prior IFN-based HCV treatment
Subsidised treatment costs the patient about A$30/month, (A$5/month for concession card holders) and this is probably as cheap as anywhere in the world.
To be balanced against the curative potential of PEG-IFN/RBV are its toxicity (flu-like symptoms, depression, anaemia, lethargy) and the requirement for contraception during and 6 months following treatment. Apart from treatment eligibility, the stage of liver disease and prognosis the genotype and viral load, presence of co-morbidities, and work and family obligations have to be considered in treatment decision-making. There needs to be at least some treatment willingness and relative socio-behavioural stability, however with persistence and good support people with relative treatment contraindications can often be successfully brought through treatment.
Greg Dore advocates some targeting of individuals with higher risk of progressive disease:
Higher likelihood of cirrhosis is predicted by:
� older age (> 40 years)
� duration of infection > 20 years
� heavy alcohol intake
� HIV or chronic HBV coinfection
� peripheral stigmata of CLD (spider naevi, palmar erythema)
� impaired hepatic synthetic function (low albumin, prolonged PT)
� AST / ALT ratio > 1.0
� AST / platelet ratio > 1.0 (<0.5 very unlikely to have cirrhosis)
At the Byrne Surgery, about 50% of people with chronic HCV met similar criteria for higher risk of HCV progression, and have been specifically targeted for treatment, with 27 people having been treated since 2003. Of 20 liver biopsies among these higher risk people, 18 had at least moderate liver fibrosis.
Although HIV and HBV co-infection are relatively uncommon in people with HCV infection, they are definite indicators of higher risk, and in many cases HCV treatment should be undertaken before HIV or HBV treatment.
Phase II trials suggest benefit from triple therapies of IFN/RBV with protease inhibitors for chronic HCV and Phase II trials are due to start soon.
Acute HCV can be treated with interferon monotherapy, with SVR rates of 80-90% in 3 months treatment, unless there is HIV co-infection or HCV genotype 1 with a high viral load. However, as about 25% of people spontaneously clear the virus (generally in the first 3 months after infection but up to 6 months and even later in a few cases) treatment of acute infection is usually deferred at least 3 months.
Although sustained viral response rates at the Byrne surgery are high (71% overall, 81% for genotype 2/3) a case was presented to show that things are not always easy. This long-term MMT patient received HCV antiviral treatment in the setting of micronodular cirrhosis, Genotype 1a/1b, viral load 360,000 and pre-treatment alcohol use of 30-60g/day. This patient was overweight 105kg, a smoker (10 cigs/day) with shortness of breath on exertion, chronic airflow limitation (not taking medications), hypertension (Enalapril), probable ischaemic heart disease (chest tightness on stress test but no ECG changes; echocardiogram: LVH with moderate dilatation), osteoarthritis (diclofenac prn), a history of peptic ulcer disease (uses omeprazole prn).
Despite these relative contraindications to treatment, this patient ceased drinking alcohol, and started combination treatment with IFN.2a/RBV, achieving rapid viral response (<600 ie qualitative RNA assay) at 5 weeks. RBV dose started with 1200mg/day and reducing to 800mg/day as haemoglobin dropped under 100, and was stopped for 5 weeks when the patient suffered severe nosebleeds (with normal BP 130/80; prothrombin time 1.1 and platelets acceptable at 81). Diclofenac was ceased, and ENT review showed a large vessel on the septum which was cauterised, packed with Chloromycetin for 3 days, with ongoing Vaseline use.
After the patient had stoically endured 36 weeks of IFN.2a/RBV, and in view of the apparent rapid viral response, treatment was stopped at week 36, sadly with a rapid ALT and viral flare. The patient has since maintained alcohol abstinence and long term low dose interferon treatment is being considered.
Issues arising from this case were the feasibility of treatment of "brittle" patients; drying of the nasal mucosa with the IFN/RBV; the pros and cons of NSAIDS for osteoarthritis in this situation; the possibility of viral escape with the interruption to RBV treatment and the wisdom of the decision to stop treatment early; whether endoscopy might have been done to exclude oesophageal varices before treatment; the benefits of going on the front foot in treating HCV in substance dependent people, who may rise to the challenge by achieving abstinence (in this case alcohol abstinence).
Other questions arising in the second half:
Q. What about treating people with persistently high-normal ALT? A: there is some discussion about whether ALT reference ranges should be lowered, especially for women. A single normal ALT measurement is not helpful, as ALT typically waxes and wanes in chronic HCV, so ongoing monitoring at least is required. Although one would rather have a persistently lowish than a persistently very high ALT, ALT correlates poorly with disease activity, and the duration of HCV is an important consideration in assessing risk of disease progression.
Q. What is the role of abdominal ultrasound in assessing chronic HCV? A: mainly to exclude portal hypertension. Greg Dore often does not order this test. Newer methods for assessing fibrosis/cirrhosis by measuring the stiffness of the liver may make ultrasound more useful.
Summary by Richard Hallinan, Greg Dore and Andrew Byrne.
3 December 2007
Editorial questions the ethics of naltrexone imlants until they are proven and registered
Degenhardt L, Gibson A, Mattick RP, Hall W. Drug and Alcohol Review 2008 27;1:1-3
Depot naltrexone use for opioid dependence in Australia: large-scale use of an unregistered medication in the absence of data on safety and efficacy.
Dear Colleagues,On page one of Drug and Alcohol Review for January 2008 there is an editorial which condemns the current practice of using customized naltrexone implants before safety and effectiveness data have been obtained. Degenhardt and co-authors reflect the sentiments of many in the field questioning the premature use of various doses of non-standardised pellets of naltrexone sub-cutaneously. After quoting the limited research and normal therapeutic safeguards, they write: �Practitioners who do so run the risk of bringing into disrepute a treatment that we think may well prove to play a useful niche role in the treatment of a small group of highly selected opioid-dependent patients.�In my view it is time to call a moratorium on this treatment. The attractive side of the interest in developing naltrexone implants is that this demonstrates the relentless efforts of researchers to develop more effective, safer and more cost effective treatments for heroin dependence. However, it is important that such a quest follow the basic rules of all medical research, always protecting those taking part in the research.Standard doses of supervised methadone in traditional clinics have always suited a substantial proportion of those addicted to street heroin. Now that we have a second variety of methadone and two types of buprenorphine in Australia, as well as better �matching� of drugs, doses, added supports, etc, these success rates have improved further. Trials utilizing both methadone and buprenorphine as appropriate have shown up to 80% retention at 6 months. About 5% will successfully detoxify each year, still leaving a proportion of drug users either unwilling or unable to cope with existing treatments. Thus these may suit other approaches such as supervised naltrexone tablets, depot injections or implants (or even heroin trials). There are still waiting lists for tradition detoxification services, both medicated and otherwise.Now that John Howard is leaving office Australia may yet get its latter-day drug trial. Even beyond a simple �heroin trial�, we may need some new bold new approaches for alcohol, amphetamine use, depression, suicide and the stresses of modern life. Just as there is some indication that naltrexone may help a certain group of addicts, there has also been some promise in the use of tiagabine, ondansetron, modafinil, long-acting morphine and dexamphetamine. A new drug, varenicline (Champix) is to be released next month on the PBS under similar conditions as Zyban. There is some unconfirmed information that this nicotinic receptor drug may reduce alcohol cravings at the same time.On the subject of the stresses of modern life, I learned of an inspiring talk at the APSAD conference in Auckland last month discussing the �search for wisdom� exemplified by Bob Cloninger in his presentation on "Wellness". This was amplified with great clarity in a lecture on the history of theism by an 89 year old retired professor of theology, Lloyd Geering. He allowed the audience to recognise that in this secular age, we are all now �playing God� ourselves and it is understandably quite stressful. My correspondent said that these �higher themes� spilled out into many of the discussions and set the tone for much of the casual interaction with colleagues at the conference, many of whom were �new� to APSAD being part of the large Kiwi contingent.
Comments by Andrew Byrne ..
26 November 2007
Is methadone cardio-protective or cardio-toxic? Probably neither.
Krantz MJ, Rowan SB, Schmittner J, Bucher Bartelson B. Physician Awareness of the Cardiac Effects of Methadone: Results of a National Survey. Journal of Addictive Diseases 2007 26;4:79-85
Dear Colleagues,
Krantz and colleagues� latest foray into the purported cardiac consequences of methadone treatment has mixed messages. Their survey of methadone clinics finds a majority of clinicians have not heard of what might be termed �Krantz syndrome�. The paper states that �only 41% (95% CI, 37- 45) were aware of methadone�s QT-prolonging properties.� Yet further: �emerging evidence suggests [methadone] may � prolong the QT interval.� But then again more forcefully: �methadone is now categorized as a medication definitively linked with torsade de pointes ��. Are they having a bet both ways on causality? The evidence on this is conflicting as Martell apparently found a significant association between dose and QT interval where Peles, Kreek et al found no such correlation, including blood levels, in a large study from Israel. Krantz and colleagues fail to cite the Peles study although it was available on the net in early December 2006.
Most reports of QT prolongation in methadone patients, eg. Pearson; Walker; Krantz; Ehret, involve (1) �mega-doses� (>300mg daily), (2) other cardio-toxic drugs, (3) abnormal metabolic states (such as hypokaloaemia) and/or (4) heart disease. Only a small minority of reported cases could be termed �regular� methadone clinic patients from my reading. And yet it is these very patients for whom Krantz gives advice to avoid methadone if possible and when it is used to avoid �high� doses.
To most dependency researchers, �high dose� means more than 100mg daily. For discussion of QT problems �high dose� would appear to mean more than 300mg daily, with the highest reports nearly 2000mg daily! The mean daily dose in Krantz� original study was 397mg; Pearson 410mg; Walker >600mg. These are not the sort of doses dependency clinics are usually familiar with.
Since so many of the cases quoted by Krantz refer to pain management, it is surprising that this survey only involved addiction centres.
This whole exercise seems to ignore the consequences of NOT giving methadone - which about 1 million people world-wide receive today. For most there is no alternative, at least none that would be affordable. Even if methadone were a cause of cardiac complications, Krantz gives us no clear strategy to prevent them, short of forgoing treatment with methadone altogether or giving lower (and therefore sometimes inadequate) doses. Hence, apart from raising anxiety levels, it is hard to see how Krantz�s long campaign on this subject has contributed to the field. It is likely that his perspective would be broadened if he had collaborated more closely with dependency specialists. The advice he is giving to the field is contrary to almost all established guidelines which stress adequate doses of methadone to reduce harmful injecting behaviour as a high priority public health strategy.
In Lancet Krantz quotes a study of methadone related deaths to justify focusing on this issue. Yet this study finds that only 4% of the deaths occurred in patients in addiction treatment programs (Ballesteros 2003), and there was absolutely nothing to suggest that cardiac effects played any role in those deaths.
It is still likely in my view that the reduced level of cocaine and heroin use with higher methadone doses shown by Dr Lisa Borg some years ago should actually protect against cardiac arrhythmias - to say nothing of the many other life-threatening concomitants of illicit heroin use, most notably overdose. Others have written about the cardio-protective effect of methadone and the opioid system in ischaemic heart disease (Marmor; Dickson).
Adding to the confusion, while stating that doctors should take account of this syndrome when prescribing methadone, Krantz still does not recommend routine ECG before starting methadone treatment. Ellen Pearson agrees with this assessment in her paper with Woosley, stating further that limiting the dose of methadone is unlikely to completely avoid cardiac complications. As far as I am aware nobody has yet reported a series of cases of cardiac arrhythmia in �normal� methadone patients, so how can this be a public health issue?
Although Pearson�s 59 FDA reports did not specify whether methadone was prescribed as part of an addiction program or otherwise, one may deduce that no more than 14 of the cases would likely have been �normal� clinic patients and only one death occurred in this group in a patient reportedly taking 29mg daily. I understand that few clinics would be able to measure out a dose of 29mg, raising the possibility that this is a mistake or a typo on the FDA report. Even as Krantz states that the FDA reports are an underestimate of the prevalence of this complication, there are still only the most sparse number of cases considering well over a million Americans have been on the treatment over the years (~240,000 currently). I also note that of 5 deaths in Pearson�s excellent report, only one of them had torsades, the fatal arrhythmia associated with QT changes, raising the possibility that there was only one cardiac death out of 59 cases over a period of years.
In my view the majority of prescribers in this survey who had not heard of QT changes were more likely to give better treatment to their patients than the �enlightened� minority who may have tried to take heed of Krantz�s sentiments.
Comments by Andrew Byrne ..
I note that of 7 web citations in this paper, 6 did not link to the correct (or indeed any) site. This may be a common problem with changes to web addresses yet it must also be a weakness of a scientific paper when peer-reviewed published citations are always to be preferred where possible in my view.
Krantz MJ, Rowan SB, Schmittner J, Bucher Bartelson B. Physician Awareness of the Cardiac Effects of Methadone: Results of a National Survey. Journal of Addictive Diseases 2007 26;4:79-85
Pearson EC, Woosley RL. QT prolongation and torsades de pointes among methadone users: reports to the FDA spontaneous reporting system. Pharmcoepidemiol Drug Saf. 2005 14;11:747-753
Martell BA, Arnsten JH, Krantz MJ, Gourevitch MN. Impact of methadone treatment on cardiac repolarization and conduction in opioid users. Am J Cardiol. 2005;95:915-8
Peles E, Bodner G, Kreek MJ, Rados V, Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients - a cross-sectional study. Addiction 2007 102;2:289-300
Ballesteros MF, Budnitz DS, Sanford CP, Gilchrist J, Agyekum GA, Butts J. Increase in Deaths Due to Methadone in North Carolina. JAMA 2003 290:40
Krantz MJ, Mehler PS. QTc prolongation: methadone's efficacy-safety paradox. Lancet 2006 368:556-557
Byrne A, Stimmel B. Methadone and QTc prolongation. Lancet 2007 369:366
Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, D. Robertson AD, Mehler PS. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med. (2002) 137:501-504
Walker PW, Klein D, Kasze L. High dose methadone and ventricular arrhythimias: a report of three cases. Pain 2003 103:321-4
Ehret GB, Voide C, Gex-Fabry M, Chabert J et al. Drug-Induced Long QT Syndrome in Injection Drug Users Receiving Methadone High Frequency in Hospitalized Patients and Risk Factors. Arch Intern Med 2006 166:1280-1287
Marmor M, Penn A, Widmer K, Levin R, Maslansky R. Coronary artery disease and opioid use. Am J Cardiol. 2004;93:1295-1297
Dickson E et al. �Runners high� may protect against myocardial infarction. Am J Physiol Heart Circ Physiol 2007; Advance online publication
20 November 2007
Management of the Narcotic Addict (Halliday R. 1963)
Below is the text for the VERY FIRST description of methadone in the treatment of addiction, two years before Dole’s publication. Note that Dr Halliday recommends 40mg in divided doses for the first three days then 30, 20 and 10mg over 12 days for detoxification with some patients needing treatment over a longer period of weeks or months under supervision and with appropriate safeguards and psychosocial support. He does not state why he recommends methadone, only that he does and in the absence of any other opioid. I have included a citation and abstract for a subsequent paper co-authored by Halliday describing their experience with methadone in Vancouver from 1959 to 1964 for both short and longer term prescribed patients. This is all insightful and way ahead of their time in my view. Yet it in no way detracts from the work of Dole and Nyswander who I understand were unaware of this work in 1963 when they were doing similar things in New York City - but without the stated aim of abstinence. AB ..
Halliday R. Management of the Narcotic Addict. 1963 British Columbia Medical Journal 5(10):412-414
In recent years there has been a change of opinion as to the nature of problems of the addict, and it is now generally accepted that the addict is a sick person physically, psychologically and socially, and as such requires medical and other treatments. The practising physician should be, as in other areas of medicine, a member of the treatment team, and it is assumed that there will be an increasing demand on his time and skill in this held of treatment.
According to Press and Parliamentary reports, the Minister of National Health and Welfare, Miss Judy La Marsh, has stated there is not any legal barrier against the prescribing of narcotics by a physician for an addicted person, provided that such treatment is directed toward withdrawal from narcotics and eventual abstinence. In other words, treatment is not to be considered as continued maintenance therapy on narcotics unless all other measures have been attempted and have failed. References are frequently made to the so-called “British System’ and it is believed that the small number of drug addicts in the United Kingdom is due to this system — the system being that of drug maintenance. This belief is erroneous and it might be pertinent at this time to state the facts since this might help to clear the confusion that exists in many people’s minds about this situation,
In 1955 Mr. J. H. Walker, who was then the United Kingdom delegate to the United Nations Narcotic Commission referred to his government’s attitude to drug addicts and their treatment in his submission to the Canadian Senate Committee enquiring into the use of narcotic drugs in Canada. He made a number of points quite clear; namely:
1. The policy of the Government was based on the recommendations of the Committee appointed in 1924, and headed by Sir Humphrey Rolleston, to advise the Ministry of Health on the implementation of the Dangerous Drugs Act. (This committee maintained, with few exceptions, addiction to morphine and heroin should be regarded as a manifestation of a morbid state, and not as a mere form of vicious indulgence), That the policy did not include the mistaken notion, held by many people, that addicts should be regularly supplied with drugs on a maintenance basis. A memorandum to physicians from the Ministry of Health included this statement: “the continued supply of drugs to a patient, either direct or by prescription, solely for the gratification of addiction is not regarded as a medical need.”
The Rolleston Committee concluded that morphine or heroin might properly be administered to addicts in the following circumstances:
(a) where patients are under treatment by the gradual withdrawal method with a view to cure;
(b) where it has been demonstrated that after a prolonged attempt at cure that the use of the drug cannot be safely discontinued entirely on account of the severity of the withdrawal symptoms produced;
(c) where it has been clearly demonstrated that the patient, while capable of leading a useful and relatively normal life when a certain minimum dose is regularly administered, becomes incapable of this when the drug is entirely discontinued.
The physician is the only person who interprets these recommendations, particularly the last one, in regard to the treatment of his patient, and it is because of misunderstanding about this that the concept of a “British System” in terms of maintenance therapy for all addicts has become a widely accepted, however erroneous, belief. This belief is another one of the legends that confuse ideas about the problem of narcotic addiction. Other legends include beliefs that British addicts are registered for treatment and that there are ‘drug clinics set up by the Government to which addicts report regularly for their drugs, either by drug supply or by prescription. Reliable investigators like Schur (2) and Brill and Larimore (3) have demonstrated that there is no such thing as a “British System” for these addicts and one agreed that the narcotic problem in the United Kingdom is a relatively minor one, largely owing to social and cultural factors rather than to superior legislative controls. The most significant and different attitude however is that of accepting the addicts as a sick person rather than a criminal.
In this country, as in the United States, the absence of community treatment facilities must he directly related to the social concept of the addict as a criminal first, and a sick person second. All available statistics from the treatment centres located in correctional institutions indicate that not more than 5% - 10% of addicts have been helped to abstain following such treatment alter a suitable follow-up period - say, 5 years. (4) One of the major drawbacks in such treatment programs, which within the institutional setting have been well developed in many instances, has been the lack of adequate follow-up and rehabilitation in the community as well as the lack of community facilities at which the addict might seek treatment in the first instance. The medical practitioner (and this is particularly true in the United States) has been threatened, and in many cases prosecuted, if he prescribed narcotics for addict patients when such patients were not in a hospital or clinic. It is true that it is extremely difficult to treat many addicts unless they are in a dosed setting such as a hospital or clinic and that ambulant treatment, as this has been practised in the past, is unsatisfactory. However it is not illegal to treat the patient on an ambulant basis. This being so, the physician may properly prescribe narcotics or other drugs for the treatment of the addict provided that such treatment is part of a more comprehensive program designed to help the addict eventually abstain from the use of narcotic drugs.
As it is not possible in most areas to admit the addict into a general or psychiatric hospital for the treatment of his addiction as such, it is suggested that the physician should do whatever he can to establish and maintain contact with the addict patients in his practice. The physician may need help from other colleagues, agencies and so on to ensure that a comprehensive treatment program is established for his patient. He can initiate a gradual withdrawal program by the administering of suitable drugs, either directly or by prescription. Such drugs may require to be dispensed on a daily basis or be given to a “sponsor” or “chaperone” where the patient is incapable of proper self administration, and this has been the practice at the Narcotic Addiction Foundation of B.C. A typical drug withdrawal program is as follows:
1.
Tabs. Methadone 10 mgms. q.i.d. x 3 days, then
10 mgms. tid. x 3 days
10 mgms. bid. x 3 days
5 mgms. bid. x 3 days
2.
Tabs. Perphenazine 4 mgms. t.i.d. 6 hourly
4 mgms. x 12 days
3.
Chloral Hydrate Grs 7½ @ H.S. x 12 days
In selected patients a more gradual withdrawal program is set up, during which the patient may have narcotics (methadone) prescribed on a continuing basis over a period of weeks or months. Such a program demands careful selection of patients who are considered to have good motivation and prospects for rehabilitation, and also requires close and continuing supervision of the therapist or therapists concerned. It follows that narcotics are not then being prescribed in such instances ‘solely for the gratification of addiction’, but are being used because they are considered to be necessary in the overall treatment of the patient. A comparable situation might be the continuing and controlled prescription of tranquillisers to severely mentally ill patients, who are thereby able to live and function in the community, rather than to be hospitalized. In the last analysis the responsible physician determines his treatment program in the light of what is considered to be sound and ethical medical practice. Some clarification on this is required from the national and provincial Colleges of Physicians and Surgeons.
During the program of withdrawal medication, whether rapid or prolonged, the medication is constantly under review, and if necessary altered to suit the patient’s needs - e.g. depression may become a prominent and severe symptom, and anti-depressants may require to be introduced to alleviate this condition.
Other needs of the patient are explored by the psychiatric and social work staff of the Narcotic Addiction Foundation, and attempts are made to understand these and to develop a suitable treatment program around meeting these or giving the patient adequate support until his problems can be dealt with in a more satisfactory manner. Where in-patient treatment is desirable, the patient is admitted to the nine bedded unit available for this purpose. With such a small number of beds delays in admission for such treatment are unavoidable.
It is intended to make further communications on this complex problem of drug addiction but it is hoped that this introductory statement may be of some help to those physicians who are interested and are anxious to participate in the treatment of this problem which has made such extensive inroads into our own community.
If further information is desired please address enquiries to:
The Narcotic Addiction Foundation of B-C.
640 West Broadway, Vancouver 9, B.C.
or Telephone TRinity 9-4585
REFERENCES
1. Proceedings of the special committee on the Traffic in Narcotic Drugs in Canada.
Queen’s Printer, Ottawa, 1955, pp. 362-363.
2. Schur, E. M. Narcotic Drug Addiction in Britain and America. Indiana University Press, 1962, p. 316.
3. Larimore, G. W. and Brill, H.
On the Site Study of the British Narcotic System Report to Governor Nelson Rockefeller, New York, 1959, pp. 23-26.
4. Pescor, M. J. Follow-up Study of Treated Narcotic Drug Addicts. U.S. Public Health Report Supplement 170, 1943, pp. 1-18.
5. Hunt, O. H. and Odoroff, M. Follow-up Study of Narcotic Drug Addicts After Hospitalization. U.S. Public Health Services Report, Volume 77, No. 1, Jan., 1962, pp. 41-54.
Paulus I, Halliday R. Rehabilitation and the Narcotic Addict: Results of a Comparative Methadone Withdrawal Program. CMAJ 1967 96:655-659
The purpose of this retrospective study was to compare (1) regular methadone withdrawal treatment and (2) prolonged methadone withdrawal treatment in 105 and 71 voluntary patients respectively, who attended the Narcotic Addiction Foundation (N.A.F.) between 1959 and mid-1964. Treatment consisted of individual counselling and medical care for all, and only residential care and psychiatric assessment for selected cases. The number of treatment sessions and the details of drug therapy are described.
One hundred and fifty-three of 176 patients (87%) were interviewed approximately one to five years after the first clinic contact. Forty-three per cent showed some overall improvement in their behaviour. Rehabilitation was defined as change in a specific area, drug use, work, criminal behaviour, community associations, friendship patterns and family relationships rather than in terms of abstention from drugs only. Age affected comparative results.
Halliday R. Management of the Narcotic Addict. 1963 British Columbia Medical Journal 5(10):412-414
In recent years there has been a change of opinion as to the nature of problems of the addict, and it is now generally accepted that the addict is a sick person physically, psychologically and socially, and as such requires medical and other treatments. The practising physician should be, as in other areas of medicine, a member of the treatment team, and it is assumed that there will be an increasing demand on his time and skill in this held of treatment.
According to Press and Parliamentary reports, the Minister of National Health and Welfare, Miss Judy La Marsh, has stated there is not any legal barrier against the prescribing of narcotics by a physician for an addicted person, provided that such treatment is directed toward withdrawal from narcotics and eventual abstinence. In other words, treatment is not to be considered as continued maintenance therapy on narcotics unless all other measures have been attempted and have failed. References are frequently made to the so-called “British System’ and it is believed that the small number of drug addicts in the United Kingdom is due to this system — the system being that of drug maintenance. This belief is erroneous and it might be pertinent at this time to state the facts since this might help to clear the confusion that exists in many people’s minds about this situation,
In 1955 Mr. J. H. Walker, who was then the United Kingdom delegate to the United Nations Narcotic Commission referred to his government’s attitude to drug addicts and their treatment in his submission to the Canadian Senate Committee enquiring into the use of narcotic drugs in Canada. He made a number of points quite clear; namely:
1. The policy of the Government was based on the recommendations of the Committee appointed in 1924, and headed by Sir Humphrey Rolleston, to advise the Ministry of Health on the implementation of the Dangerous Drugs Act. (This committee maintained, with few exceptions, addiction to morphine and heroin should be regarded as a manifestation of a morbid state, and not as a mere form of vicious indulgence), That the policy did not include the mistaken notion, held by many people, that addicts should be regularly supplied with drugs on a maintenance basis. A memorandum to physicians from the Ministry of Health included this statement: “the continued supply of drugs to a patient, either direct or by prescription, solely for the gratification of addiction is not regarded as a medical need.”
The Rolleston Committee concluded that morphine or heroin might properly be administered to addicts in the following circumstances:
(a) where patients are under treatment by the gradual withdrawal method with a view to cure;
(b) where it has been demonstrated that after a prolonged attempt at cure that the use of the drug cannot be safely discontinued entirely on account of the severity of the withdrawal symptoms produced;
(c) where it has been clearly demonstrated that the patient, while capable of leading a useful and relatively normal life when a certain minimum dose is regularly administered, becomes incapable of this when the drug is entirely discontinued.
The physician is the only person who interprets these recommendations, particularly the last one, in regard to the treatment of his patient, and it is because of misunderstanding about this that the concept of a “British System” in terms of maintenance therapy for all addicts has become a widely accepted, however erroneous, belief. This belief is another one of the legends that confuse ideas about the problem of narcotic addiction. Other legends include beliefs that British addicts are registered for treatment and that there are ‘drug clinics set up by the Government to which addicts report regularly for their drugs, either by drug supply or by prescription. Reliable investigators like Schur (2) and Brill and Larimore (3) have demonstrated that there is no such thing as a “British System” for these addicts and one agreed that the narcotic problem in the United Kingdom is a relatively minor one, largely owing to social and cultural factors rather than to superior legislative controls. The most significant and different attitude however is that of accepting the addicts as a sick person rather than a criminal.
In this country, as in the United States, the absence of community treatment facilities must he directly related to the social concept of the addict as a criminal first, and a sick person second. All available statistics from the treatment centres located in correctional institutions indicate that not more than 5% - 10% of addicts have been helped to abstain following such treatment alter a suitable follow-up period - say, 5 years. (4) One of the major drawbacks in such treatment programs, which within the institutional setting have been well developed in many instances, has been the lack of adequate follow-up and rehabilitation in the community as well as the lack of community facilities at which the addict might seek treatment in the first instance. The medical practitioner (and this is particularly true in the United States) has been threatened, and in many cases prosecuted, if he prescribed narcotics for addict patients when such patients were not in a hospital or clinic. It is true that it is extremely difficult to treat many addicts unless they are in a dosed setting such as a hospital or clinic and that ambulant treatment, as this has been practised in the past, is unsatisfactory. However it is not illegal to treat the patient on an ambulant basis. This being so, the physician may properly prescribe narcotics or other drugs for the treatment of the addict provided that such treatment is part of a more comprehensive program designed to help the addict eventually abstain from the use of narcotic drugs.
As it is not possible in most areas to admit the addict into a general or psychiatric hospital for the treatment of his addiction as such, it is suggested that the physician should do whatever he can to establish and maintain contact with the addict patients in his practice. The physician may need help from other colleagues, agencies and so on to ensure that a comprehensive treatment program is established for his patient. He can initiate a gradual withdrawal program by the administering of suitable drugs, either directly or by prescription. Such drugs may require to be dispensed on a daily basis or be given to a “sponsor” or “chaperone” where the patient is incapable of proper self administration, and this has been the practice at the Narcotic Addiction Foundation of B.C. A typical drug withdrawal program is as follows:
1.
Tabs. Methadone 10 mgms. q.i.d. x 3 days, then
10 mgms. tid. x 3 days
10 mgms. bid. x 3 days
5 mgms. bid. x 3 days
2.
Tabs. Perphenazine 4 mgms. t.i.d. 6 hourly
4 mgms. x 12 days
3.
Chloral Hydrate Grs 7½ @ H.S. x 12 days
In selected patients a more gradual withdrawal program is set up, during which the patient may have narcotics (methadone) prescribed on a continuing basis over a period of weeks or months. Such a program demands careful selection of patients who are considered to have good motivation and prospects for rehabilitation, and also requires close and continuing supervision of the therapist or therapists concerned. It follows that narcotics are not then being prescribed in such instances ‘solely for the gratification of addiction’, but are being used because they are considered to be necessary in the overall treatment of the patient. A comparable situation might be the continuing and controlled prescription of tranquillisers to severely mentally ill patients, who are thereby able to live and function in the community, rather than to be hospitalized. In the last analysis the responsible physician determines his treatment program in the light of what is considered to be sound and ethical medical practice. Some clarification on this is required from the national and provincial Colleges of Physicians and Surgeons.
During the program of withdrawal medication, whether rapid or prolonged, the medication is constantly under review, and if necessary altered to suit the patient’s needs - e.g. depression may become a prominent and severe symptom, and anti-depressants may require to be introduced to alleviate this condition.
Other needs of the patient are explored by the psychiatric and social work staff of the Narcotic Addiction Foundation, and attempts are made to understand these and to develop a suitable treatment program around meeting these or giving the patient adequate support until his problems can be dealt with in a more satisfactory manner. Where in-patient treatment is desirable, the patient is admitted to the nine bedded unit available for this purpose. With such a small number of beds delays in admission for such treatment are unavoidable.
It is intended to make further communications on this complex problem of drug addiction but it is hoped that this introductory statement may be of some help to those physicians who are interested and are anxious to participate in the treatment of this problem which has made such extensive inroads into our own community.
If further information is desired please address enquiries to:
The Narcotic Addiction Foundation of B-C.
640 West Broadway, Vancouver 9, B.C.
or Telephone TRinity 9-4585
REFERENCES
1. Proceedings of the special committee on the Traffic in Narcotic Drugs in Canada.
Queen’s Printer, Ottawa, 1955, pp. 362-363.
2. Schur, E. M. Narcotic Drug Addiction in Britain and America. Indiana University Press, 1962, p. 316.
3. Larimore, G. W. and Brill, H.
On the Site Study of the British Narcotic System Report to Governor Nelson Rockefeller, New York, 1959, pp. 23-26.
4. Pescor, M. J. Follow-up Study of Treated Narcotic Drug Addicts. U.S. Public Health Report Supplement 170, 1943, pp. 1-18.
5. Hunt, O. H. and Odoroff, M. Follow-up Study of Narcotic Drug Addicts After Hospitalization. U.S. Public Health Services Report, Volume 77, No. 1, Jan., 1962, pp. 41-54.
Paulus I, Halliday R. Rehabilitation and the Narcotic Addict: Results of a Comparative Methadone Withdrawal Program. CMAJ 1967 96:655-659
The purpose of this retrospective study was to compare (1) regular methadone withdrawal treatment and (2) prolonged methadone withdrawal treatment in 105 and 71 voluntary patients respectively, who attended the Narcotic Addiction Foundation (N.A.F.) between 1959 and mid-1964. Treatment consisted of individual counselling and medical care for all, and only residential care and psychiatric assessment for selected cases. The number of treatment sessions and the details of drug therapy are described.
One hundred and fifty-three of 176 patients (87%) were interviewed approximately one to five years after the first clinic contact. Forty-three per cent showed some overall improvement in their behaviour. Rehabilitation was defined as change in a specific area, drug use, work, criminal behaviour, community associations, friendship patterns and family relationships rather than in terms of abstention from drugs only. Age affected comparative results.
10 November 2007
Lancet items relating to cannabis regulation versus cannabis harms
Dear Colleagues,
Degenhardt, Hall and colleagues� Lancet letter is the only one this week to be classified �premium content� and thus is not available to casual �browsers� like myself. Yet once read, it seems to be almost the last word on the subject of cannabis harms. This debate has been raging in England since 1995 when Lancet famously wrote: �The smoking of cannabis, even long term, is not harmful to health.� This was both incorrect and unhelpful in a difficult area needing clarity, not bland over-simplifications. In the past, Hall has written similar sentiments � but in a more guarded and scientific manner along the lines of �For a majority of users, cannabis causes few if any adverse health consequences.� But this is a long way from saying it is harmless.
And from the current state of knowledge, summarised in this week�s insightful letters, we can now say confidently that the legal status of cannabis is not related to the rate of its use, harmful or otherwise. To quote: �Cannabis use changed at similar rates across States irrespective of these [differing] penalties. This finding strongly suggests that other factors - such as social attitudes and perceived harms - are more important drivers of consumption than penalties for use.� Regarding Australian jurisdictions, �about half have criminal penalties for possession or use, and the remainder have fines�.
As Degenhardt and colleagues rightly state, more serious than the small risk of psychosis is the 16% risk of dependence in young people using cannabis. Further, as Macleod points out in his letter, respiratory symptoms both from tobacco mixed with cannabis and even cannabis alone, also loom large as good reasons to advise young people to avoid cannabis.
Degenhardt L, Hall WD, Roxburgh A, Mattick RP. UK classification of cannabis: is a change needed and why? Lancet 2007 370:1541
Zullino DF, Rathelot T, Khazaal Y. Cannabis and psychosis. Lancet 2007; 370:1540
Macleod J, Oakes R, Copello A, et al. The psychosocial sequelae of use of cannabis and other illicit drugs by young people: systematic review of longitudinal, general population studies. Lancet 2004; 363: 1579-1588
Moore THN, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370: 319-328 http://www.thelancet.com/journals/lancet/article/PIIS0140673607611623/abstract
Editorial. Rehashing the evidence on psychosis and cannabis. Lancet 2007; 370:292 http://www.thelancet.com/journals/lancet/article/PIIS0140673607611337/fulltext
http://www.thelancet.com/journals/lancet/article/PIIS0140673607611350/fulltext
Degenhardt, Hall and colleagues� Lancet letter is the only one this week to be classified �premium content� and thus is not available to casual �browsers� like myself. Yet once read, it seems to be almost the last word on the subject of cannabis harms. This debate has been raging in England since 1995 when Lancet famously wrote: �The smoking of cannabis, even long term, is not harmful to health.� This was both incorrect and unhelpful in a difficult area needing clarity, not bland over-simplifications. In the past, Hall has written similar sentiments � but in a more guarded and scientific manner along the lines of �For a majority of users, cannabis causes few if any adverse health consequences.� But this is a long way from saying it is harmless.
And from the current state of knowledge, summarised in this week�s insightful letters, we can now say confidently that the legal status of cannabis is not related to the rate of its use, harmful or otherwise. To quote: �Cannabis use changed at similar rates across States irrespective of these [differing] penalties. This finding strongly suggests that other factors - such as social attitudes and perceived harms - are more important drivers of consumption than penalties for use.� Regarding Australian jurisdictions, �about half have criminal penalties for possession or use, and the remainder have fines�.
As Degenhardt and colleagues rightly state, more serious than the small risk of psychosis is the 16% risk of dependence in young people using cannabis. Further, as Macleod points out in his letter, respiratory symptoms both from tobacco mixed with cannabis and even cannabis alone, also loom large as good reasons to advise young people to avoid cannabis.
Comments by Andrew Byrne ..
Degenhardt L, Hall WD, Roxburgh A, Mattick RP. UK classification of cannabis: is a change needed and why? Lancet 2007 370:1541
Zullino DF, Rathelot T, Khazaal Y. Cannabis and psychosis. Lancet 2007; 370:1540
Macleod J, Oakes R, Copello A, et al. The psychosocial sequelae of use of cannabis and other illicit drugs by young people: systematic review of longitudinal, general population studies. Lancet 2004; 363: 1579-1588
Moore THN, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370: 319-328 http://www.thelancet.com/journals/lancet/article/PIIS0140673607611623/abstract
Editorial. Rehashing the evidence on psychosis and cannabis. Lancet 2007; 370:292 http://www.thelancet.com/journals/lancet/article/PIIS0140673607611337/fulltext
http://www.thelancet.com/journals/lancet/article/PIIS0140673607611350/fulltext
8 November 2007
Drug and Alcohol Dependence, December 2007. Some interesting titles.
Alcoholic monkeys, clinic accreditation, ‘antagonists’ fail opiate and cocaine users (again), methadone success in US prisoners, buprenorphine/benzo interactions and hep C.
Dear Readers,
Some of you have written to enquire after my health. In fact my internet silence in recent weeks is due to the wasteful, costly and time consuming exercise of practice accreditation. Most health care providers are now subject to this exaction, yet few such interventions could be less productive than for addiction treatment providers in New South Wales. We are routinely assessed by well meaning people who have never written a prescription. Imagine a pharmacy or fire brigade being accredited by non-pharmacists or non-fire officers?! And there is no determination as to whether the right patients are getting the right dose of the right drug! That is a state Health Department responsibility, we are told, yet there is only one single inspector for the entire state! Sadly many addiction patients in NSW receive relatively poor care. Some receive inadequate doses and no access to take-away doses, contrary to the Federal treatment guidelines’ advice that such dosing improves outcomes significantly where used appropriately.
So getting back to a list of meaty scientific titles has been a great pleasure, this time the December edition of Drug and Alcohol Dependence, the largest circulation American addiction publication.
It is nice to see familiar names coming up in the research literature. Some one has never met, others one may have met at conferences, others still have become real friends over the years. In this edition alone we find Cicero, Grabowski, Mitchell TB, Lintzeris, Ciraulo, Strang, Schwartz RP, Dolan, Dore, Westcott, Wodak, Vlahov, Inciardi, Degenhardt, Grulich, Kaldor, Kippax, McCance-Katz, Comer and Nunes. This is a breathtaking array of scientific talent and it is quite something that they would all be represented in a single edition of a medical journal.
Several titles immediately caught my eye so I glanced at their abstracts. Hence I would advise those interested to obtain the full article where appropriate. As ever, there are repetitive themes popular with funding authorities despite usually come up with the same outcomes. Many do not learn from history and keep trying the same thing, hoping for different results. Albert Einstein said this was a form of madness.
Various medications have been tried in cocaine users but researchers seem to ignore the fact that most cocaine users are in for a good time. As such, they are unlikely to continue with a drug which gives them a ‘bad time’ (reserpine makes many normal people feel ill, so why give it to cocaine users?). Likewise the same group from the University of Cincinnati, tried tiagabine in yet another costly RCT with no significant difference (placebo does not give much of a predictable ‘good time’ either!).
Next we learn of yet another study showing that oral naltrexone does not work for relapse prevention in heroin users. Yet this new observational study, with some ethical issues to my mind, shows one marginally interesting finding. The failure rate of 70% in those who ‘tested the block’ (relapsed while still taking the naltrexone) was even worse in those who had waited for the block to wear off where a 90% drop-out rate was found. Is this a joke? Or are 70-90% failure rates encouraging enough to warrant more research?
Next we have a report of what should be the very last RCT of methadone treatment, this time in pre-release prisoners in Baltimore. Jail inmates have never been considered quite the same as others regarding medical and psychiatric needs in many parts of the world, including China, Russia, Cuba and America. So now we know that methadone also ‘works’ in pre-release prisoners. And even American prisoners … surprise, surprise! This was introduced into NSW prisons over 20 years ago, initially as a pre-release measure like in this trial. It has consistently produced enormous benefits for the entire community at very modest cost. Along with some other quite backward things in our state, this is one innovation we can be proud of and which is now being slowly copied around the world.
Next we have a fascinating item in which mature monkeys were found to enjoy alcohol with flavouring and to cut down their voluntary intake significantly when accompaniments were altered. Shades of ice-pops and mixers. Hence there seem to be some parallels between us and our close animal cousins. Again, no real surprise here, but gratifying confirmation that humans are not completely unique freaks in the animal kingdom in our desire to be ‘high’.
A group from Australia has done a careful study of the chronological march of the hepatitis C epidemic with very little good news to date. Despite harm reduction measures, treatment availability, education, etc, Australia still has a major public health problem with up to 9,000 new cases each year. More effective interventions might reduce this, as with HIV to hundreds or even dozens.
Another item looks at over 1000 gay men and finds that each year, about 5% started at least once weekly amphetamine use with the same proportion taking up at least once weekly MDMA (ecstasy) use. The proportions would have been very different 10 years ago when ecstasy use would probably have been much more popular. But we now live in the ‘ice age’ as Walter Ling calls it, where Pam Lichty calls it the ‘drug for today’ (which it is!). Yet few researchers have really addressed stimulant use in a logical manner, looking unemotionally at the harms and benefits as perceived by the users and to society generally. This is extraordinary when these drugs have been used across the world for generations now. Anabolic steroids probably fit into the same category and because of their often illicit or unprescribed nature, research is extremely limited and thus advice to the many users of these drugs is necessarily perfunctory: ‘say no to drugs’, keep fit, don’t share needles, don’t use too much, use with a friend, use an injecting room, etc.
Lastly there are two items on drug interactions. We have what might be the first serious report of a significant buprenorphine interaction. Some buprenorphine patients developed sedation on anti-retroviral drugs and needed dose reductions. This is just normal therapeutics, but nice to see it formally reported by a clinical experiment rather than happenstance. Lintzeris reports on giving 20mg diazepam or placebo to methadone or buprenorphine patients in a small RCT with variations in the opioid as well. He concludes: ‘High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine’. No great surprise here, either.
Comments by Andrew Byrne ..
http://www.redfernclinic.com/
http://www.sciencedirect.com/science/journal/03768716
Winhusen T, Somoza E, Ciraulo DA, Harrer JM, Goldsmith RJ, Grabowski J, et al. A double-blind, placebo-controlled trial of tiagabine for the treatment of cocaine dependence. Drug and Alcohol Dependence 2007 91;2-3:141-148
Winhusen T, Somoza E, Sarid-Segald O, Goldsmith JR,,,. A double-blind, placebo-controlled trial of reserpine for the treatment of cocaine dependence. Drug and Alcohol Dependence 2007 91;2-3:205-212
Sullivan MA, Garawi F, Bisaga A, Comer SD,,,Nunes EV. Management of relapse in naltrexone maintenance for heroin dependence. Drug and Alcohol Dependence 2007 91;2-3:289-292
Kinlock TW, Gordon MS, Schwartz RP, O’Grady K, Fitzgerald TT, Wilson M. A randomized clinical trial of methadone maintenance for prisoners: Results at 1-month post-release. Drug and Alcohol Dependence 2007 91;2-3:220-227
Katner SN, Von Huben SN, Davis SA, et al. Robust and stable drinking behavior following long-term oral alcohol intake in rhesus macaques. Drug and Alcohol Dependence 2007 91;2-3:236-243
Razali K, Thein HH, Bell J, Cooper-Stanbury M, Dolan K, Dore G et al. Modelling the hepatitis C virus epidemic in Australia. Drug and Alcohol Dependence 2007 91;2-3:228-235
Prestage G, Degenhardt L, Jin F, Grulich A, Imrie J, Kaldor J, Kippax S. Predictors of frequent use of amphetamine type stimulants among HIV-negative gay men in Sydney, Australia. Drug and Alcohol Dependence 2007 91;2-3:260-268
McCance-Katz EF, Moody DE ,,,. Interaction between buprenorphine and atazanavir or atazanavir/ritonavir. Drug and Alcohol Dependence 2007 91 2-3:269-278
Lintzeris N, Mitchell TB, Bond AJ, Nestor L, Strang J. Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients. Drug and Alcohol Dependence 2007 91;2-3:187-194
31 October 2007
Lord Howe Island - a naturalist's observations at North Bay
North Bay (Mount Eliza in background)
Written by Andrew Byrne, October 07
We were shown North Bay by Ian Hutton, naturalist and now local resident of Lord Howe Island. The first thing we saw was a lazy (or perhaps sick) turtle about 400mm shell diameter, lying on the sand as we arrived by boat across the lagoon.
Ball's Pyramid
We walked to a clearing where Mr Hutton used some laminated cards to demonstrate the geologic formation of the island millions of years ago. It seems that like Hawaii in more modern times, a weakness in the earth's crust allowed a series of volcanic eruptions under the sea as the Pacific and Australian tectonic plates moved slowly against each other. There were four of five such eruptions in a line from up near Bougainville, including Middleton and Elizabeth Reefs, Lord Howe Island and Balls Pyramid to the south. The same crust weakness has now migrated to a point 400km south of Lord Howe and shows little if any current volcanic under-sea activity. We were told that a similar, parallel line of undersea mountains exist between this chain and the Australian east coast, known mainly to fishermen who are aware that the nutrients pushed up by the currents attend a much better range and quantity of fish than in the open fallow Pacific ocean.
The Old Gulch at low tide
We were shown an undersea map of the island which was remarkable in that nearly all of the raised 'land' was submerged at current sea levels with only 2-3% exposed at the island we know today. Likewise, there was a large sea channel between the island and Balls Pyramid, showing that the two were separate islands caused by different volcanic eruptions.
To demonstrate the nature of the formation of the island, we were taken to the 'Old Gulch' which is a rocky inlet about 300 metres across a sandy isthmus from North Bay beach. Here, on either side of a mass of smooth weathered stones, we saw seams of dark igneous rock penetrating the coarse conglomerate where cooling contraction had occurred. The regular geometric patterns of such chemical 'crystalisation' was clearly shown, some forming rough hexagons as in the famous Irish coastal formation.
Seaweed eating sea urchin
Next we found two beautiful sea urchin shells. They were of two distinct species, each related to the common 5 pointed starfish. The round one lived off seaweed and had 5 concentric teeth around a central mouth which masticated the food. The mouth apparatus could be extracted from the broken shell revealing a remarkable pearly and symmetrical structure Mr Hutton told us was called the 'lantern of Aristotle'. The other ovoid urchin is rarely ever seen alive since it spends most of its time below the sand. Still with the 5 sectors, an off-centre mouth took in quantities of sand which it sifted to extract the nutrients while the waste sand was excreted. The mollusc was propelled along by short, stiff hairs all over its 100mm body. Urchin eggs are eaten by various Pacific peoples who consider them a delicacy. They are called 'ooni' in Japan.
Sand eating sea urchin
One of the children found a dead crab on the beach. Mr Hutton said it was paradoxically called a 'double headed crab'. While looking like a normal baby crab, it was originally used as bait for catching the prized LHI 'double-headed fish'. The crab lives in burrows during the day, eating most of the litter left on the beach when it comes out at night (it was mostly seaweed and blue bottles that day). A large limb of driftwood blown up onto the sand was covered in so-called 'goose barnacles'. No relation to geese or barnacles, they were in fact an extraordinary variety of solitary crab which lived its whole life in a double baby clam shell, bound to the host wood by a strong attachment thread.
We were then given a tutorial on bluebottles. These singular creatures have two common varieties in the waters of Lord Howe. The ones we associate with long stinging tendrils, 'Man-o-war' species, feed on small fish or other animals which get paralysed and then raised up to the body where they are digested. The smaller bluebottle variety 'by-the-wind sailor' has both right and left handed square-rig 'sails' and are thus wind propelled in two different directions - and amazing evolutionary advantage. They have short stingers aimed at tiny organisms floating in the water. Blue bottles normally breed in huge colonies mid-ocean and these can be several kilometres across. Being propelled only by the sea and wind, the island never has bluebottles on both sides at the one time.
The island's sands are made up of 100% corals and shells in contrast to mainland sand with over 50% silica, quartz and other non-organic elements. The latter is best for building and so, for construction on the island it is imported, like almost everything else.
We now turned our attention to birds, not upwards, but downwards as the first species we encountered were nesting right there on the sand! Due to the absence of humans or other predators, most native species show a total lack of fear. 'Wild cats', introduced in the 1800s, have now been eradicated, finally allowing the return of ground nesting birds on the main island. Goats were also finally removed, allowing the return of much of the native vegetation.
Sooty tern with egg (up to 24% of its own weight)
Our sand nestlings were 'Sooty terns' with their enormous eggs, being up to 25% of their body weight. White terns, Black Noddys, buff-banded rails and the Emerald Dove were other common species, the latter having deep green iridescent British racing green middle plumage. Currawongs are also common and they have a habit of dive bombing unsuspecting tourists. A small local kingfisher is smaller than the kookaburra.
In June 1834 permanent settlement of the island began with three Englishmen and their Maori wives. They initially hunted mutton birds whose burrows are still seen all around the island. Some of the grandest Norfolk Island Pines date from this time. A stand of them at North Bay were apparently planted by school children in the 1930s. There is an active plan to rid the island of non-native trees and all saplings have been cut down. Helping this move, local nesting birds? droppings have burned the foliage below, killing the trees in some cases.
Lord Howe Island was named after Richard Howe, first Lord of the British Admiralty. It was first sighted by Europeans (or possibly by any human beings) in 1788 by HMS Supply, captained by Henry Lidgbird Ball. His name was given to the volcanic pinnacle 16 km south of the main island as Balls Pyramid (apostrophes were eliminated from all Australian place names in the middle of the 20th century). Highly recommended, especially if you can get a frequent flyer booking or a package deal off season.
Written by Andrew Byrne following a relaxing week on the island in October 2007.
More references: http://en.wikipedia.org/wiki/Lord_Howe_Island Lord Howe Island from the summit of Mt Gower |  Mt Lidgbird and Mt Gower in cloud |
 Mt Gower from Old Settlement beach. Island Trader just visible |  Mt Lidgbird (777m) and Mt Gower (875m) |
 Typical forest track with Kentia Palms |  Masked booby |
The extended family at 80th birthday
of John Justinian Byrne
(minus Peter & Allan) 2006
of John Justinian Byrne
(minus Peter & Allan) 2006
Last year's family T-shirt emblem
Looking towards North Bay and Mt Eliza
13 September 2007
Tobacco associated with new mental illness in prospective study.
Smoking is associated with first-ever incidence of mental disorders: a prospective population-based study. Cuijpers P, Smit F, ten Have M, de Graaf R.
Addiction 2007 102:1303-9
Dear Colleagues,
This month�s Addiction journal contains a most important study, almost hidden at the back of an issue packed with other meaty items. For the first time, I believe, the intrepid Dutch group (NEMESIS or Netherlands Mental Health Survey and Incidence Study) has found a significant association between tobacco smoking and mental illness. With up to 80% response rates in over 5000 Dutch adults this study looked at who was smoking and/or had a mental illness at the start, one and three years (along with many other variables).
A significant association found was between smoking and the development of anxiety, dysthymia and new alcohol abuse. Unlike cannabis, no association was found with psychosis. Considering the prevalence of smoking the findings are still highly significant. The prospective nature and accounting for confounders in these findings supports a causal association from the tobacco, yet no dose relation was found. Hence further research will need to look at these areas, according to the authors. Also, a rational pathogenic pathway from smoking to mental disease needs to be confirmed. It may not be a coincidence that some mental illness is increasing in extent and severity in certain countries.
Two other recent studies have apparently shown links between smoking and dementia (Holland; ANU). The Erasmus Medical Centre in Holland found a 50% increase in dementia in age matched smokers. The links with lung cancer and arterial disease are well known. An Adelaide hospital has apparently restricted elective surgery for those who continue to smoke. This month�s Addiction journal reports the same thing from the NHS in Leicester, England (p1331). Yet another report in this issue points to equal outcomes for those who quit abruptly and those who cut down gradually (Hughes p1326).
So the ground-swell against tobacco continues, based on its being the largest single reversible cause of death and morbidity in our society. Over 19,000 Australians die each year from tobacco related illnesses. While we know how to treat established nicotine addiction, we still do not know why people smoke and whether there are safer pharmaceutical alternatives and when these may be appropriate. One innovation which should be considered in Australia is the oral tobacco wad (�chewing tobacco� or Swedish �snus�) which may offer more advantages than harms, although it probably just as addictive as the smoked variety.
Comments by Andrew Byrne ..
Van Laar M, van Dorsselaer S, Monshouwer K, de Graaf R. Does cannabis use predict the first incidence of mood and anxiety disorders in the adult population? Addiction 2007 102:1251-1260
11 September 2007
Methadone works if used properly
http://www.bmj.com/cgi/content/extract/335/7618/464-a
Letters
Drug misusers and incentives
Methadone works if used properly
Stevenson, a senior British forensic doctor, observes that methadone treatment does not work, contrary to 40 years of high quality research showing that it does.1
The reason can be found in the lack of adherence to evidence based clinical guidelines in much of the United Kingdom.2 With some notable exceptions, UK addicts are routinely given dose schedules that are contrary to guidelines (such as mean doses of less than 40 mg daily in place of double that found in well run clinics). These advise strict dose supervision for new and unstable patients with an effective dose range from 60 mg to 120 mg daily after careful induction starting with no more than 40 mg daily.3
Hong Kong, Australia, and New Zealand may be the only places where methadone has been available for over 30 years under reasonably open access and with a largely evidence based approach. Uniquely, all three have very little HIV in their large injecting populations. Few would believe this is coincidental (although hepatitis C has been a different and as yet unanswered story).
The question of whether addicts should receive incentives in treatment should be decided by practical research, not moralist opinions.4 5 Methadone treatment is already one of the most cost effective things we do in medicine and probably compares with washing hands. It would seem logical to raise the abysmal standards of practice in the UK and then examine incentives to improve results still further if needed.
Andrew Byrne, private addictions physician
75 Redfern Street, Redfern, NSW 2016, Australia
ajbyrne@ozemail.com.au
_____
Competing interests: AB charges a fee for administration of drugs in the treatment of addiction.
References
1. Stevenson RJ. Drug misusers are likely to abuse the system. BMJ 2007;335:317. (18 August.)
2. Strang J, Sheridan J, Hunt C, Kerr B, Gerada C, Pringle M. The prescribing of methadone and other opioids to addicts: national survey of GPs in England and Wales. Br J Gen Pract 2005;515: 444-51.
3. Strang J. Drug misuse and dependence-guidelines on clinical management. London: Department of Health, 1999. www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digit alasset/dh_4078198.pdf
4. Burns T. Is it acceptable for people to be paid to adhere to medication? Yes. BMJ 2007;335:232. (4 August.)
5. Shaw J. Is it acceptable for people to be paid to adhere to medication? No. BMJ 2007;335:233. (4 August.)
Rapid Responses:
http://www.bmj.com/cgi/eletters/335/7618/464-a
BMJ 2007;335:464 (8 September), doi:10.1136/bmj.39317.563600.80
Letters
Drug misusers and incentives
Methadone works if used properly
Stevenson, a senior British forensic doctor, observes that methadone treatment does not work, contrary to 40 years of high quality research showing that it does.1
The reason can be found in the lack of adherence to evidence based clinical guidelines in much of the United Kingdom.2 With some notable exceptions, UK addicts are routinely given dose schedules that are contrary to guidelines (such as mean doses of less than 40 mg daily in place of double that found in well run clinics). These advise strict dose supervision for new and unstable patients with an effective dose range from 60 mg to 120 mg daily after careful induction starting with no more than 40 mg daily.3
Hong Kong, Australia, and New Zealand may be the only places where methadone has been available for over 30 years under reasonably open access and with a largely evidence based approach. Uniquely, all three have very little HIV in their large injecting populations. Few would believe this is coincidental (although hepatitis C has been a different and as yet unanswered story).
The question of whether addicts should receive incentives in treatment should be decided by practical research, not moralist opinions.4 5 Methadone treatment is already one of the most cost effective things we do in medicine and probably compares with washing hands. It would seem logical to raise the abysmal standards of practice in the UK and then examine incentives to improve results still further if needed.
Andrew Byrne, private addictions physician
75 Redfern Street, Redfern, NSW 2016, Australia
ajbyrne@ozemail.com.au
_____
Competing interests: AB charges a fee for administration of drugs in the treatment of addiction.
References
1. Stevenson RJ. Drug misusers are likely to abuse the system. BMJ 2007;335:317. (18 August.)
2. Strang J, Sheridan J, Hunt C, Kerr B, Gerada C, Pringle M. The prescribing of methadone and other opioids to addicts: national survey of GPs in England and Wales. Br J Gen Pract 2005;515: 444-51.
3. Strang J. Drug misuse and dependence-guidelines on clinical management. London: Department of Health, 1999. www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digit alasset/dh_4078198.pdf
4. Burns T. Is it acceptable for people to be paid to adhere to medication? Yes. BMJ 2007;335:232. (4 August.)
5. Shaw J. Is it acceptable for people to be paid to adhere to medication? No. BMJ 2007;335:233. (4 August.)
Rapid Responses:
http://www.bmj.com/cgi/eletters/335/7618/464-a
A Toast to the Family, By STANTON PEELE
The following piece was sent to me by the author. It was originally published in the Wall Street Journal and brings out some basic common sense from the myth and hype which is often found in the addictions area.
A Toast to the Family
By STANTON PEELE
August 31, 2007; Page A9
Florida, Michigan and New Hampshire are some of a growing number of states to enact laws holding parents accountable for underage drinking at their homes. These laws typically involve hosting parties where alcohol is served to minors.
The target is parents who blithely allow keg parties in their basements and then let the teenagers who attend them drive home drunk. One such couple in Deerfield, Ill., was recently convicted when two 18-year-olds died in a car accident after such a party. Earlier this month, Karen Dittmer was arrested for allowing her 18-year-old son and his friends to drink beer at her birthday barbecue in New York's Suffolk County.
What kind of parents would ever allow their children to drink at home? Doesn't this put youngsters at risk?
The answer to the first question is simple. Most of the state laws include a specific exemption for children drinking at home during family and religious ceremonies. Observant Jews, for example, traditionally serve children small glasses of wine during Friday night Sabbath ceremonies. Other cultures also begin socializing children into drinking at an early age -- including Mediterranean societies such as Italy, Greece and Turkey (and non-Mediterranean societies such as China).
As for the second, two international surveys -- one conducted by the World Health Organization -- revealed that these Mediterranean countries and Israel had the lowest binge drinking rates among European adolescents.
In societies where children drink with their parents, this typically means giving a kid a small amount of wine or other alcohol, often watered down on special occasions or a family dinner. Many European countries also lower the drinking age for children when they are accompanied by parents. In the United Kingdom, for example, the legal age is 18, but for a family at a restaurant it is 16. In France and Italy, where the legal age is 16, there is no age limit for children drinking with parents.
But what might all of this mean for teen drinking problems in America?
Several studies have shown that the younger kids are when they start to drink, the more likely they are to develop severe drinking problems. But the kind of drinking these studies mean -- drinking in the woods to get bombed or at unattended homes -- is particularly high risk.
Research published in the Journal of Adolescent Health in 2004 found that adolescents whose parents permitted them to attend unchaperoned parties where drinking occurred had twice the average binge-drinking rate. But the study also had another, more arresting conclusion: Children whose parents introduced drinking to the children at home were one-third as likely to binge.
"It appears that parents who model responsible drinking behaviors have the potential to teach their children the same," noted Kristie Foley, the principal author of the study. While the phrasing was cautious, the implication of the study's finding needs to be highlighted: Parents who do not introduce children to alcohol in a home setting might be setting them up to become binge drinkers later on. You will not likely hear this at your school's parent drug- and alcohol-awareness nights.
Obviously, if a parent isn't comfortable consuming alcohol -- for whatever reason -- he or she is going to find it difficult to teach a child moderate social drinking. Fair enough. But neither should parents feel guilty or intimidated about responsibly introducing their children to alcohol in a home setting. The research suggests that this is more likely, not less, to protect the kids against the excessive drinking that permeates American high schools and colleges.
The youngest of my three children attends New York University, in a metropolis that is no stranger to alcohol. But alcohol is not forbidden fruit, since Anna drank wine at home. She says binge drinking holds no allure. I believe her.
Mr. Peele, a psychologist, therapist and attorney, is the author of several books on addiction, including the just-published "Addiction-Proof Your Child" (Three Rivers Press).
A Toast to the Family
By STANTON PEELE
August 31, 2007; Page A9
Florida, Michigan and New Hampshire are some of a growing number of states to enact laws holding parents accountable for underage drinking at their homes. These laws typically involve hosting parties where alcohol is served to minors.
The target is parents who blithely allow keg parties in their basements and then let the teenagers who attend them drive home drunk. One such couple in Deerfield, Ill., was recently convicted when two 18-year-olds died in a car accident after such a party. Earlier this month, Karen Dittmer was arrested for allowing her 18-year-old son and his friends to drink beer at her birthday barbecue in New York's Suffolk County.
What kind of parents would ever allow their children to drink at home? Doesn't this put youngsters at risk?
The answer to the first question is simple. Most of the state laws include a specific exemption for children drinking at home during family and religious ceremonies. Observant Jews, for example, traditionally serve children small glasses of wine during Friday night Sabbath ceremonies. Other cultures also begin socializing children into drinking at an early age -- including Mediterranean societies such as Italy, Greece and Turkey (and non-Mediterranean societies such as China).
As for the second, two international surveys -- one conducted by the World Health Organization -- revealed that these Mediterranean countries and Israel had the lowest binge drinking rates among European adolescents.
In societies where children drink with their parents, this typically means giving a kid a small amount of wine or other alcohol, often watered down on special occasions or a family dinner. Many European countries also lower the drinking age for children when they are accompanied by parents. In the United Kingdom, for example, the legal age is 18, but for a family at a restaurant it is 16. In France and Italy, where the legal age is 16, there is no age limit for children drinking with parents.
But what might all of this mean for teen drinking problems in America?
Several studies have shown that the younger kids are when they start to drink, the more likely they are to develop severe drinking problems. But the kind of drinking these studies mean -- drinking in the woods to get bombed or at unattended homes -- is particularly high risk.
Research published in the Journal of Adolescent Health in 2004 found that adolescents whose parents permitted them to attend unchaperoned parties where drinking occurred had twice the average binge-drinking rate. But the study also had another, more arresting conclusion: Children whose parents introduced drinking to the children at home were one-third as likely to binge.
"It appears that parents who model responsible drinking behaviors have the potential to teach their children the same," noted Kristie Foley, the principal author of the study. While the phrasing was cautious, the implication of the study's finding needs to be highlighted: Parents who do not introduce children to alcohol in a home setting might be setting them up to become binge drinkers later on. You will not likely hear this at your school's parent drug- and alcohol-awareness nights.
Obviously, if a parent isn't comfortable consuming alcohol -- for whatever reason -- he or she is going to find it difficult to teach a child moderate social drinking. Fair enough. But neither should parents feel guilty or intimidated about responsibly introducing their children to alcohol in a home setting. The research suggests that this is more likely, not less, to protect the kids against the excessive drinking that permeates American high schools and colleges.
The youngest of my three children attends New York University, in a metropolis that is no stranger to alcohol. But alcohol is not forbidden fruit, since Anna drank wine at home. She says binge drinking holds no allure. I believe her.
Mr. Peele, a psychologist, therapist and attorney, is the author of several books on addiction, including the just-published "Addiction-Proof Your Child" (Three Rivers Press).
4 September 2007
Rats alive! Alcohol reductions possible with adequate buprenorphine doses.
Biological Psychiatry 2007 61:4-12
Buprenorphine Reduces Alcohol Drinking Through Activation of the Nociceptin/Orphanin FQ-NOP Receptor System. Ciccocioppo R, Economidou D, Rimondini R, Sommer W, Massi M, Heilig M.
Dear Colleagues,
In spite of the title, this rat experiment showed both significant increases (at low doses) and decreases (at high doses) in alcohol consumption with the use of buprenorphine injected intraperitoneally 1� hours before access to alcohol. Four dose levels ranged over 3+ orders of magnitude from 0.03 to 6mg/kg. Additional experimental conditions included the use of pre-treatment naltrexone which predictably blocked some of the increased alcohol consumption while using �the selective NOP receptor antagonist UFP-101� in two similar dose ranges abolished the suppression of drinking at the higher range dose level of buprenorphine administration.
While there may be relevant receptor issues here, clinicians will be more interested in the behavioural findings and their relevance to humans. Hence these detailed rodent experiments show two quite separate outcomes: (1) the consumption of alcohol, food and liquids and (2) deductions as to the reasons behind these observations based on changes when certain blockers are used. Cicciocioppo, Heilig and colleagues� conclusions about why these rats drank more or less alcohol are well beyond my field. Further, they are of limited interest clinically at the present time.
Sinclair reported the addition of morphine reducing alcohol consumption in rats many years ago (Nature 1973) and 14 years later wrote an editorial in BMJ about the feasibility of using drugs for alcoholism. We now use effective anti-craving drugs which are not psychoactive themselves (acamprosate and naltrexone for example). Tennant reported a possible link between increasing methadone levels and reducing alcohol use in a small study (n=18). Unfortunately, this has not yet been replicated, despite its simplicity and apparent significance.
By my raw calculations the experimental dose levels used in these rat studies translated to a 70kg person would equate to 2mg, 20mg, 200mg and 400mg as single doses. These are all well above the normal therapeutic range for analgesic use (0.2-0.8mg) although the lower two doses are well within the range used in dependency treatments (doses vary from about 1mg to 32mg daily). The high doses (200 and 400mg) are supratherapeutic and could be fatal, especially in combination with alcohol as given here. Such doses are not realistic in humans, being cumbersome to administer while the cost may be over $100 daily. Evidently no rat died in this study and the lead author believes that this may be due to the hyposensitivity of Sardinian rats to opioids and other depressants.
The study of drug �replacement� is still in its infancy but already it is clear that some opioid users become stimulant users and vice versa (see Darke 1999). Equally, some alcoholics largely cease alcohol use once they �discover� opioids. Others, probably a certain minority, continue to consume both drugs.
At the same time, this study reminds us that inadequate doses of buprenorphine will limit its usefulness. This is the same as penicillin, cortisone, insulin or any other medication. And the consequences from excessive dosing in a supervised treatment setting are usually limited to minor sedation, causing the patient to seek a dose decrease or simply to miss days.
Comments by Andrew Byrne ..
References:
Sinclair JD, Adkins J, Walker S. Morphine-induced suppression of voluntary alcohol drinking in rats. Nature (1973) 246: 425-427
Sinclair JD. The feasibility of effective psychopharmacological treatments for alcoholism. British Journal of Addiction (1987) 82: 1213-1223
Tennant FS. Inadequate Plasma Concentrations in Some High-Dose Methadone Maintenance Patients. Am J Psychiatry 1987; 144: 1349-1350.
Darke S, Kaye S, Ross J. Transitions between the injection of heroin and amphetamines. Addiction 1999 94:1795-1803
31 August 2007
Pharmacy fees for methadone and buprenorphine treatments.
Drug Alc Review 2007 26;4:411-416
The impact of community pharmacy dispensing fees on the introduction of buprenorphine - naloxone in Australia. Winstock AR, Lea T, Ritter A.
Dear Colleagues,
These authors have survey responses from over 400 NSW pharmacists about current and proposed prices for methadone and buprenorphine under various regimens including daily, weekly, fortnightly and monthly attendance. A figure of $31 weekly recurs with little variation according to the number of attendances until this reached one per fortnight when the lowest response was $19 per week.
These authors do not examine these fees in relation to other commercial aspects of community pharmacy, nor are we given an international comparison. Ideally, as with other medical treatments, those who are unemployed or indigent should be looked after in the public system. In many areas there is simply no alternative to pharmacy treatment since most hospital pharmacies steadfastly refuse to become involved. In the 1980s, the published recommended price in NSW was $5 daily �including counselling� ($35 per week). Pharmacists still charge approximately the same price which is a philanthropy without parallel in health care in my experience.
The authors state that the introduction of the bup-naloxone combination product: �permitted the revision of takeaway policies � and � the possibility of unsupervised treatment.� Only one of the 24 references refers to the combination product which hardly supports the contention that this constitutes a �new treatment paradigm�. They suggest a need for: �early dissemination of unambiguous information regarding the introduction of a new medication, especially where supervised dispensing through community pharmacies is essential to the provision of treatment. The potential impact upon the successful rollout of a new treatment paradigm that was developed to benefit stable patients in the community may be jeopardised when such processes are not followed.�
I would suggest that the only thing jeopardising this new treatment paradigm being rolled-out (hate those terms!) is a lack of evidence that it actually works in practice. There is a dearth of research on both the combination product itself and on (completely) non-supervised treatment such as is commonly used in France and England. This all makes the tone of the paper somewhat confusing since the benefits proposed for buprenorphine-naloxone are still theoretical.
These authors appear to believe that long term dispensing or administration of buprenorphine should be cheaper than traditional short term maintenance treatments and they seem disappointed with outcomes showing otherwise, at least for less than fortnightly attendance.
It is hard to be �unambiguous� about a new and untried treatment, and pharmacists of all people, know that dealing with addictions can be tough and unpredictable. Also, the new proposal assumes that doctors are able to distinguish which patient is going to be stable long term, yet there is no simple way I know of doing that. The best protection for patients may be the innate conservatism of Australian health care workers, sceptical of claims made for new drugs until proven in practice. It is indeed a �brave new world�, giving addicted patients medication without the continuing supervision of a pharmacist, nurse, psychologist or even a self-help or group therapy session. In fact, this �paradigm� flies in the face of the DSM definition of addiction, involving some degree of loss of control over drug use at certain times.
Another concern was borne out in a paper from Melbourne recently (Neilsen 2007) where administering buprenorphine as a sub-lingual tablet was associated with numerous reported practical problems compared with the use of liquid methadone. I wonder how many Australian doctors are prescribing unsupervised buprenorphine.
Comments by Andrew Byrne ..
References: Nielsen S, Dietze P, Dunlop A, Muhleisen P, Lee N, Taylor D. Buprenorphine supply by community pharmacists in Victoria, Australia: perceptions, experiences and key issues identified. Drug Alc Review 2007 26;2:143-152
30 August 2007
Perceptive correction on some mythology around alcoholism and addictions
This is a perceptive �correction� on some mythology around alcoholism and addictions by a man with decades of experience in the field.
Wall Street Journal
Bad Advice for Lindsay Lohan
By STANTON PEELE August 7, 2007; Page A11
People have been offering advice to Lindsay Lohan since she relapsed soon after leaving her last stint of rehab. Now that she's entering another clinic, it's time to reevaluate many of these recommendations. Following are the four main mistaken pieces of advice:
1) Ms. Lohan should never, ever drink again. Her father, Michael Lohan, agrees with the treatment programs his daughter has tried and believes that she should never, ever drink again. The elder Lohan swore off alcohol himself not long ago, after a serious car accident led to a drunk-driving conviction. Although this advice is well-intended, it is implausible. What are the chances Ms. Lohan will abstain for the rest of her life? After her second stint in rehab, wearing an alcohol monitor, she lasted about a week before partying all night.
The alternative view is that the 21-year-old Ms. Lohan will almost surely drink again and she needs a fallback position to be safe. This might include having her "people" shut her off from drinking too much, or setting a departure time for leaving clubs or parties. Failing this, someone -- if not Ms. Lohan herself -- needs to keep her from driving after she's been drinking. That way, she can at least survive to try to do better down the road.
2) Ms. Lohan needs to learn that she is a lifetime alcoholic-addict. She inherited the alcoholism-addict gene from her father, right? The alternative position is: Who knows that is true?
Another young Hollywood star who was branded an addict was Drew Barrymore. Remember when she appeared on the cover of People magazine at age 13 as America's youngest addict? Ms. Barrymore had many substance abusing relatives, including her parents, and so experts concluded she would be addicted her entire life.
But, almost 20 years later, in 2007, Ms. Barrymore was on the cover of People again -- this time as the world's most beautiful person! No one thinks of her as an addict any longer. Young people often ultimately outgrow youthful problems, sometimes quite serious ones, including drinking and drug addiction.
3) Ms. Lohan needs to remain locked in treatment for a long time, with no day passes. Critics note that Ms. Lohan was permitted out of her treatment program to go to her gym. Other addicts, such as Daniel Baldwin, tut-tut that this is too permissive. Mr. Baldwin should know -- he's been in treatment nine times. In his 40s when last treated, he now claims to be off cocaine for good.
On the other hand, maybe it is no wonder Ms. Lohan and so many others relapse after being restricted in residential programs for months. The minute the doors of the center shut behind them, they are out on the street facing the same old playmates and playgrounds.
An alternative approach would be to treat Ms. Lohan as an outpatient. This offers her the opportunity to expose herself to the world under supervision. She could then practice how to deal with her freedom while maintaining her sobriety. For example, she could be guided towards new friends and ways of spending her free time. Of course neither the hospital nor the outpatient setting can work miracles right away -- it took Drew Barrymore years to reform her life.
4) Ms. Lohan should avoid show business. The problem obviously is her involvement in movies, coupled with all of Tinsel Town's temptations. If she just stays away from Hollywood and the glitterati, she'll be fine.
But Ms. Barrymore didn't need to leave Hollywood to change. The alternative view is that Ms. Lohan is a talented person who can achieve success in movies and music, and that work is therapeutic. Not all her films are great. But she has done good work with the likes of legendary director Robert Altman and co-stars Kevin Kline, Meryl Streep and Lily Tomlin. More opportunities like these could help her to learn professionalism, discipline and self-respect.
Ms. Lohan needs to grow up, realize her talents and find ways to fill her time that aren't self-destructive. Coming to see herself as an adult, accepting responsibility, and developing pride in her skills are difficult but time-tested therapeutic techniques. These are things Ms. Lohan won't learn in standard treatment programs.
Mr. Peele is a psychologist and therapist who has written nine books on addiction. His new book is "Addiction-Proof Your Child" (Three Rivers Press).
Wall Street Journal
Bad Advice for Lindsay Lohan
By STANTON PEELE August 7, 2007; Page A11
People have been offering advice to Lindsay Lohan since she relapsed soon after leaving her last stint of rehab. Now that she's entering another clinic, it's time to reevaluate many of these recommendations. Following are the four main mistaken pieces of advice:
1) Ms. Lohan should never, ever drink again. Her father, Michael Lohan, agrees with the treatment programs his daughter has tried and believes that she should never, ever drink again. The elder Lohan swore off alcohol himself not long ago, after a serious car accident led to a drunk-driving conviction. Although this advice is well-intended, it is implausible. What are the chances Ms. Lohan will abstain for the rest of her life? After her second stint in rehab, wearing an alcohol monitor, she lasted about a week before partying all night.
The alternative view is that the 21-year-old Ms. Lohan will almost surely drink again and she needs a fallback position to be safe. This might include having her "people" shut her off from drinking too much, or setting a departure time for leaving clubs or parties. Failing this, someone -- if not Ms. Lohan herself -- needs to keep her from driving after she's been drinking. That way, she can at least survive to try to do better down the road.
2) Ms. Lohan needs to learn that she is a lifetime alcoholic-addict. She inherited the alcoholism-addict gene from her father, right? The alternative position is: Who knows that is true?
Another young Hollywood star who was branded an addict was Drew Barrymore. Remember when she appeared on the cover of People magazine at age 13 as America's youngest addict? Ms. Barrymore had many substance abusing relatives, including her parents, and so experts concluded she would be addicted her entire life.
But, almost 20 years later, in 2007, Ms. Barrymore was on the cover of People again -- this time as the world's most beautiful person! No one thinks of her as an addict any longer. Young people often ultimately outgrow youthful problems, sometimes quite serious ones, including drinking and drug addiction.
3) Ms. Lohan needs to remain locked in treatment for a long time, with no day passes. Critics note that Ms. Lohan was permitted out of her treatment program to go to her gym. Other addicts, such as Daniel Baldwin, tut-tut that this is too permissive. Mr. Baldwin should know -- he's been in treatment nine times. In his 40s when last treated, he now claims to be off cocaine for good.
On the other hand, maybe it is no wonder Ms. Lohan and so many others relapse after being restricted in residential programs for months. The minute the doors of the center shut behind them, they are out on the street facing the same old playmates and playgrounds.
An alternative approach would be to treat Ms. Lohan as an outpatient. This offers her the opportunity to expose herself to the world under supervision. She could then practice how to deal with her freedom while maintaining her sobriety. For example, she could be guided towards new friends and ways of spending her free time. Of course neither the hospital nor the outpatient setting can work miracles right away -- it took Drew Barrymore years to reform her life.
4) Ms. Lohan should avoid show business. The problem obviously is her involvement in movies, coupled with all of Tinsel Town's temptations. If she just stays away from Hollywood and the glitterati, she'll be fine.
But Ms. Barrymore didn't need to leave Hollywood to change. The alternative view is that Ms. Lohan is a talented person who can achieve success in movies and music, and that work is therapeutic. Not all her films are great. But she has done good work with the likes of legendary director Robert Altman and co-stars Kevin Kline, Meryl Streep and Lily Tomlin. More opportunities like these could help her to learn professionalism, discipline and self-respect.
Ms. Lohan needs to grow up, realize her talents and find ways to fill her time that aren't self-destructive. Coming to see herself as an adult, accepting responsibility, and developing pride in her skills are difficult but time-tested therapeutic techniques. These are things Ms. Lohan won't learn in standard treatment programs.
Mr. Peele is a psychologist and therapist who has written nine books on addiction. His new book is "Addiction-Proof Your Child" (Three Rivers Press).
8 August 2007
Implants of naltrexone: information sought on outcomes
Dear Readers,
Like many of my colleagues, I am concerned at the use of naltrexone implants for addiction purposes in Australia without the normal safeguards of a new medication. As an alternative to post-marketing surveillance I propose a survey to seek first hand reports of experiences, both positive and negative, with these devices. Some have been used in patients who have travelled long distances and may lack sufficient local medical support.
Readers who have consulted with patients who have been prescribed naltrexone implants are invited to write to report their findings, including individual case reports. Age and sex of patients and dependency diagnosis would be useful, along with any other relevant clinical details (type of implant, number of implants, etc).
I undertake to collate these and report back to the appropriate parties, including health authorities, manufacturers (where these are known), informants and patient groups for their information.
In medicine, �proof of effectiveness� means that a sufficient number of positive research trials of high quality have been published by reputable authors in peer reviewed, respected journals.
In my view we have not yet reached this situation by general consensus with naltrexone implants.
With best regards,
Potential conflict of interest: In my practice I prescribe and dispense methadone, buprenorphine and other drugs in the treatment of addictions. I have published on methadone to abstinence experience in my own medical practice (ref on request).
Like many of my colleagues, I am concerned at the use of naltrexone implants for addiction purposes in Australia without the normal safeguards of a new medication. As an alternative to post-marketing surveillance I propose a survey to seek first hand reports of experiences, both positive and negative, with these devices. Some have been used in patients who have travelled long distances and may lack sufficient local medical support.
Readers who have consulted with patients who have been prescribed naltrexone implants are invited to write to report their findings, including individual case reports. Age and sex of patients and dependency diagnosis would be useful, along with any other relevant clinical details (type of implant, number of implants, etc).
I undertake to collate these and report back to the appropriate parties, including health authorities, manufacturers (where these are known), informants and patient groups for their information.
In medicine, �proof of effectiveness� means that a sufficient number of positive research trials of high quality have been published by reputable authors in peer reviewed, respected journals.
In my view we have not yet reached this situation by general consensus with naltrexone implants.
With best regards,
Andrew Byrne ..
Potential conflict of interest: In my practice I prescribe and dispense methadone, buprenorphine and other drugs in the treatment of addictions. I have published on methadone to abstinence experience in my own medical practice (ref on request).
Subscribe to:
Posts (Atom)